Process for the preparation of citric acid

ABSTRACT

IT IS DISCLOSED THAT CITRIC ACID OR ITS SALTS ARE OBTAINED BY THE HYDROLYSIS OF A 3-CARBAMOYL-3-HYDROXY-4-CYANOBUTYRIC ACID OR SALT, THAT A 3-CARBAMOYL-3-HYDROXY-4CYANOBUTYRIC ACID OR SALT IS OBTAINED FROM A 3-CARBAMOYL3,4-EPOXYBUTYRIC ACID OR SALT, THAT A 3-CARBAMOYL-3,4EPOXYBUTYRIC ACID OR SALT, IS OBTAINED FROM A 3-CARBAMOYL3-HYDROXY-4-HALOBUTYRIC ACID OR SALT, THAT A 3-CARBAMOYL3-HYDROXY-4-HALOBUTYRIC ACID IS OBTAINED FROM A 3-CYANO3-HYDROXY-4-HALOBUTYRIC ACID OR SALT, THAT A 3-CYANO-3HYDROXY-4-HALOBUTYRIC ACID OR SALT IS OBTAINED FROM A 3OXO-4-HALOBUTYRIC ACID OR SALT, THAT A 3-OXO-4-HALOBUTYRIC ACID OR SALT IS OBTAINED FORM A 3-OXO-4-HALOBUTYRYL HALIDE, AND THAT A 3-OXO-4-HALOBUTYRYL HALIDE IS OBTAINED FROM DIKETENE. PREFERRED HALIDE COMPOUNDS ARE COMPOUNDS OF CHLORINE.

oct. 3o, 1973 K. E"W|EGAND PROCESS FOR THE PREPARATION OF CITRIC ACIDFiled Aug. 18, 1971 l72 Sheets-Sheet l NON Efo @25M Get. 30, 1973 l K.E. WIEGAND 3,769,337

PROCESS FOR THE PREPARATION OF CITRIC ACID Filed Aug. 18, 1971 2Sheets-Sheet 2 WATER- cN+ H+or I+- B CIH) C D -Lh REACTING L+ L REACTING-Ln' FIG- 3- FIC. 4.

BASE-i (BASIC) BASE (cAlom- F-v-(CN) E CONVERTINC IM) IIR) A cONvERTINGGIM) -f-v REACTING REACTINC u@ (BASIC) '6j I-SALT I9/ FIG. 8.

MINERAL ACID or BASE i C K(H)(M)(R) La I-IYDROLYsIs L FIG. 9.

ACID or BASE- ACID or BASE- (H)(M)(R) L+ HYDROLYSING [H r HYDROLYSING -LFIG. IO.

United States Patent O M 3,769,337 PROCESS FOR THE PREPARATION F CITRICACID Karl E. Wiegand, Baton Rouge, La., assignor to Ethyl Corporation,Richmond, Va. Filed Aug. 18, 1971, Ser. No. 172,627 Int. Cl. C07c 59/16U.S. Cl. 260--535 P 28 Claims ABSTRACT 0F THE DISCLOSURE It is disclosedthat citric acid or its salts are obtained by the hydrolysis of a3-carbamoyl-3-hydroXy-4-cyanobutyric acid or salt, that a3-carbamoyl-3-hydroxy-4- cyanobutyric acid or salt is obtained from a3-carbamoyl- 3,4-epoxybutyric acid or salt, that a 3carbarnoyl3,4epoxybutyric acid or salt is obtained from a 3-carbamoyl-3hydroxy-4halobutyric acid or salt, that a 3-carbamoyl-3-hydroXy-4-halobutyric acid is obtained from a 3-cyano-3-hydroxy-4-halobutyric acid or salt, that a 3-cyano-3-hydroXy-4-halobutyric acid or salt is obtained from a 3-oxo-4-halobutyric acid or salt, that a 3-oxo-4-halobutyric acid or saltis obtained from a 3-oxo-4-halobutyryl halide, and that a3-oxo-4-halobutyryl halide is obtained from diketene. Preferred halidecompounds are compounds of chlorine.

BACKGROUND 0F THE INVENTION Field of the invention The invention relatesto the preparation of citric acid and of salts of citric acid.

Description of the lprior art Citric acid or its salts are useful indifferent ways as exemplified by the following patents: as aplasticizer, U.S. Pat. 2,409,703; as a bleaching agent, U.S. P'at.2,529,831; as a food antioxidant, U.S. Pat. 2,563,855; as a detergentcomponent, U.S. Pat. 2,765,280.

The principal prior sources of citric acid and its derivatives arerecovery from natural products such as citrus fruits and production viamicological or fermentation processes. The recovery of citric acid fromnatural products or sources is disclosed in U.S. Pats. 2,027,264;2,193,904; and 2,396,115. The production of citric acid by micologicalprocesses is disclosed in U.S. Pats. 2,353,- 771; 2,739,923; 2,883,329and 3,335,067.

Heretofore the chemical synthesis of citric acid or of its salts hasproved to be very difficult. In fact, the only -known U.S. patentrelating to a chemical synthesis of citric acid is 3,356,721 whichissued in 1967 and there is nothing in the patent to show that asignificant yield of citric acid or its salts is obtained with theprocess described therein. Since the amount of natural source citricacid is limited, there has been a need in the art for a commerciallyattractive chemical synthesis process for producing citric acid or itssalts.

OBJECTS It is an object of the present invention to provide a processfor synthesizing citric acid and salts of citric acid from readilyavailable moderate cost raw materials.

Another object of the present invention is to provide process operationsfor producing compositions which are useful intermediates for thesynthesis of citric acid and salts of citric acid.

Another object of the present invention is to provide a process forproducing intermediate compositions that can be hydrolyzed to producecitric acid or its salts in high yield.

Another object of the present inventioniis to provide a process forproducing the intermediate compositions of 3,769,337 Patented Oct. 30,1973 the preceding object Ivia the cyanide cleavage of the epoxy groupof a 3-carbamoyl-3,4epoxybutyric acid or a salt or ester thereof to form3carbamoyl-3-hydroXy-4-cyanobutyric acid, or a salt or ester thereof.

Another object of the present invention is to provide a process forproducing 3-carbamoyl-3,4epoxybutyric acid or a salt or ester thereoffrom a 3-carbamoyl-3-hydroXy-4-halobutyric acid, or a salt or esterthereof.

Another object of the present invention is to provide a process forproducing a 3-carbamoyl-3-hydroXy-4-halobutyric acid or a salt or esterthereof from a 3-cyano-3- hydroXy-4-halobutyric acid or a salt or esterthereof.

Another object of the present invention is to provide a process forproducing a 3-cyano-3-hydroxy-4-halobutyric acid or a salt or esterthereof from a 3oxo4halobutyric acid or a salt or ester thereof.

Another object of the present invention is to provide a process forproducing 3-oxo-4-halobutyric acid by a water hydrolysis of a3-oxo-4-halobutyrylhalide.

Other and further objects and features of the present invention willbecome apparent upon a careful consideration of the following discussionand the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES FIG. l shows in block form a preferredembodiment of the features of the present invention whereby citric acidor its salts or esters are produced from diketene via a sequenceinvolving several novel reactions which provide preferred ways toproduce and utilize the several intermediate compositions involved inthe overall process.

FIG. 2 shows a portion of the process of FIG. 1 whereby a particularlyuseful intermediate composition; viz,3-carbamoy1-3-hydroxy-4-halobutyric acid, or a salt or ester thereof isconverted to citric acid or a salt thereof by three process stepsinvolving 1) epoxidation with halogen elimination of a3-carbamoyl-3-hydroxy4-halobutyric acid to form a3-carbamoyl-3,4-epoxybutyric acid derivative. (2) cyanide scission ofthe epoxy group of the 3-carbamoy1-3,4-epoxybutyric acid derivative toform a 3-carbamoyl-3-hydroXy-4-cyanobutyric acid derivative and (3)hydrolysis of the 3-carbamoyl-3-hydroxy-4- cyanobutyric acid derivativeto produce citric acid or a salt thereof.

FIG. 3 illustrates a process for producing 3-oxo-4-halobutyric acid by awater hydrolysis of 3-oxo-4-halobutyryl halide.

FIG. 4 shows a process for producing 3-cyano-3-hydroxy-4-halobutyricacid from 3-oXo-4-halobutyric acid by a cyanohydrination reaction in anHCN system.

FIG. 5 shows a process for hydrolyzing 3-cyano-3-hydroXy-4-halobutyricacid to produce 3carbamoyl3hy droxy-4-halobutyric acid.

FIG. 6 shows a process for the epoxidatibn of3-carbamoyl-3-hydroXy-4-halobutyric acid to form an epoxide derivativethereof. l

FIG. 7 shows an epoxide scission process whereby the epoxy structure ofthe epoxide derivative of B-carbamoyl- 3-hydroxy-4-halobutyric acid isconverted to a 3-carbamoyl-3-hydroxy-4-cyanobutyric acid compound.

FIG. 8 shows a coordinated combination of the two steps of FIGS. 6 and 7to indicate a particularly significant subcombination of the overallprocess.

FIG. 9 indicates separately a hydrolysis process whereby a.3-carbamoyl-3-hydroxy-4-cyanobutyric acid compound is converted to acitric acid compound.

FIG. 10 illustrates the plural step hydrolysis of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid compounds to produce one or moreintermediate compounds in a first step and then to convert saidintermediates to citric acid compounds in a subsequent step.

3 SUMMARY oF THE INVENTION The present invention provides, inter alia, amethod of producing citric acid and its salts from 3-oxo-4-halobutyrylhalide.

the corresponding free acid before performing the next reaction, Viz,hydrolysis. On hydrolysis, the 3-cyano-3- hydroxy-4-halobutyric acidproduces S-carbamoyl-S-hydroxy-4-ha1obutyric acid which readilyeliminates halogen when placed in a basic system to form a S-Carbamoyl-In accordance with one embodiment of this invention 5 3,4-ep0xybutyricacid Salt, The 3carbam0y13,4epoxy- 3-0X0-4-hal0lgutyry1 halide, whichmay be readily formed butyric acid salt is treated with cyanide tc causecleavage by halogenatlon of dlketene, 1s hydrolyzed t o produce 3- ofthe epoxy ring thereby forming a 3-carbam0y1.3 hy OXO- i-halebutyrleaeld Whleh 1S reacted Wlth hydrogen droxy-ecyanobutyric acid vsalt whichon hydrolysis in acid cyanide to produce3-cyano-3-hydroxy-Li-halobutyrlc acld. 10 or basic media yields citricacid or salts of citric acid If metal lons are present 1n the system 1nwhlch this cyadepending on whether acidic or basic conditions are emnidereaction is performed so that a salt of 3-cyan0-3-hyployed inthehydrolysis operation, droXy-4-halobutyric acid is or tends to be formed,the The foregoing process sequence may be represented by system ispreferably acidiiied to convert any such salt to the following series ofequations:

(1) (l |Ol Hydrolysis H H XCHzCCHzCX (acidt2 base, or preferably XCHzCCHzC-OH Wa er 3oxo4halobutyryl halide where X=halogen (F, C1, Br, I),

preferably C1 3-oxo-4-halobutyric acid (2) Il H Hydrocyanation O H XCHZCCHzC-OH (Nitrile formation) XCHztJ-C H2O-0H 3-eyano-3hydroxy4halobutyricacid (or salt thereof) (for 3-oxo-4-halobutyric acid preferred cationssee equation (4)) (a) (Init H Hydrolysis (|)H u XCH2(]CH2COH (Preferablywater) XCHzC-CH2COH CN O=CNH 3-cyano3l1ydroxy4halobutyric acid3-carbamoy1-3-hydroxy-4-haiobutyric acid (4) ([3H H Epoxidation OH OXCH2C-CH2C-0H with base (MOH, M20, [l

M2003, MHCOB); MOH CHr--C-CHzC-OM O=CNH1 preferred, NaOH esp.

3-carbamoy1-3-hydroxy-4-halobutyric acid 3-carbamoyl3,4epoxybutyric acidsalt where M=alkali metal (Li, Na, K, Rb, Cs), preferably Na; oralkaline earth metal (1/2) (Be, Mg, Ca, Sr, Ba), preferably Ca); orammonium NH4".

(5) 0 Epoxide scission (|)H 3H Il HCN or MCN, preferablyNC-CHz-C--CHzC-OM CH2CC HzC-OM NaCN or KCN (pH 8-14) (T=550 C.) (1-20hours) O= NH2 O=CNH2 3-carbamoyl3,4epoxybutyric acid salt3-carbamoy1-3-hydroxy-4-cyanobutyc acid salt 6(8) $13'. Il Hydrolysis 3H(I)I NCCHzC-CHzC OM (acid) HOCCHzC-CHzC-OH O= NH2 O=C O HS-earbamoyl--hydroXy-i-cyanobutyric acid salt Citric acid ?H il?Neutralization u (I)H n HOCCHzC-CHzC-OH (base) MOCCHZCCHzC-OM O=C 0H 0=COM Citrio acid Citric acid salt 6(b) (l) H [I Partial hydrolysis u (|)HNC CHzC-CHzC OM (base) (pH=l3.0) (T=25 HzN-C CHiC-CHzC-OM 35 C.) (Time2-50 hrs.) O--CNHz O=CNH2 3carbamoyl-S-hydroxy-myanobutyrlc acid salt3-hydroxy3,4dicarbamoylbutyrc acid salt Hydrolyss (base) (pH= OH13.5-14) T=2535 C. for Il 24-48 hrs., then up to MO-C CHzCCHzC-OM 100 C.for 5-25 hours O=CNH2 Hydrolysis 3-carbamoyl-S-hydroxyglutaric acid saltIl l Il MO C CHzC CHzC--OM O=C OM Citric acid Salt (base) (pH 13-14)(T=40 100 C.) (Time 10-30 hrs.)

The foregoing process is subject to numerous variations. Thus althoughthe reactions are preferably conducted in an aqueous environment or inaqueous solution, it is possible to employ suitable anhydrous organicreaction media including protic solvents in some of these reactions.Conversions between the acid and salt forms provide ways to enhancepurification and by-product removal as well as to provide stableintermediates for storage or more convenient transportation tosubsequent processing. Also in some instances, the use as reactants ofesters rather than acids or salts facilitates handling and the selectionof solvent systems. Thus, the fundamental processing steps discussed maybe supplemented by form changing steps (i.e., neutralizations,saponifications, esteriications, ester hydrolysis, etc.), purificationsteps, drying steps or the like. Further, although the process is mostpreferably conducted on a continuous basis in an unbroken sequence, i-tis feasible to perform the process on a batch or semibatch basis andalso to interrupt the processing sequence operations, e.g. by storing ortransporting intermediates for subsequent use in the succeeding processsteps. In addition, in many instances several of the reactions describedmay be conducted concurrently or sequentially in a single environment toappear as a single processing step, while single reactions may beconducted in a staged manner to appear as several processing steps.

Inasmuch as this process is subject to numerous variations, thefollowing are some of the process embodiments disclosed or provided bythis invention.

(A) Converting 3 carbamoyl-3-hydroxy4halobutyric acid or salt or esterthereof to a salt or ester of 3car bamoyl3,4epoxybutyric acid by areaction with a base, converting the salt or ester of3-carbamoyl-3,4epoxy butyric acid to a salt or ester of3-carbamoyl-3-hydroxy- 4-cyanobutyric acid via reaction with cyanide,and hydrolyzing the salt or ester of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid to produce citric acid or salt thereof.

(B) Hydrolyzing the cyano group of 3-cyano-3-hydroxy-4-halobutyric acidor a salt or ester thereof preferably with water at a pH equal to the pHof a solution of 3-carbamoyl-3-hydroxy-4-halobutyric acid to produce 3-carbamoyl-3-hydroxy-4-halobutyric acid or an ester thereof and thenperforming process (A).

(C) Subjecting 3-oxo-4-halobutyric acid or a salt or ester thereof toreaction with hydrogen cyanide or a salt thereof to produce3-cyano-3-hydroxy-4-halobutyric acid or a salt or ester thereof, andthen performing process (B).

(D) Hydrolyzing 3-oxo-4-halobutyryl halide to produce3-oxo-4-halobutyric acid or a salt or ester thereof, and then performingprocess (C).

(E) Reacting 3-oxo-4-chlorobutyryl chloride with water to produce3-oxo-4-chlorobutyric acid, reacting 3-oxo- 4-chlorobutyric acid withammonium, alkali metal or alkaline earth metal ions and with cyanideions in an aqueous system to produce a salt of 3-oxo-4-chlorobutyricacid and HCN and reacting the salt of 3-oxo-4-chlorobutyric acid withHCN to form a salt of 3-cyano-3-hydroxy-4-chlorobutyric acid, acidifyingthe salt of 3-cyano- 3-hydroxy-4-chlorobutyric acid with mineral acid toproduce 3-cyano-3-hydroxy-4-chlorobutyric acid and an alkali metal saltor an alkaline earth metal salt, solvent extracting the3-cyano-3-hydroxy-4-chlorobutyric acid to recover the acid from thealkali metal or alkaline earth metal salt and recovering the acid fromthe solvent, hydrolyzing the recovered 3-cyano-3-hydroxy-4-chlorobutyricacid to produce 3-carbamoyl-3-hydroxy-4-chlorobutyric acid, convertingthe 3carbamoyl3-hydroxy-4-chlorobutyric acid to a salt of3-carbamoyl-3,4-epoxybutyric acid by reaction with a base, reacting thesalt of 3-carbamoyl-3,4epoxybutyric acid with mineral acid to convertthe salt to an acid structure forming 3-carbamoyl- 3,4cpoxybutyric acidand a salt of the mineral acid and of the base reacted in the precedingstep, recovering the 3-carbamoyl-3,4epoxybutyric acid, converting the3car bamoyl3,4epoxybutyric acid to a salt of 3-carbam0yl-3-hydroxy-4-cyanobutyric acid by reacting the acid with ammonium, alkalimetal or alkaline earth metal ions and with cyanide ions in an aqueoussystem at a pH of from about 8 to about 14, and hydrolyzing the salt of3-carbamoyl-3-hydroxy-4-cyanobutyric acid with a hydroxide, oxide,carbonate or bicarbonate of an alkali metal or alkaline earth metal orammonium hydroxide or carbonate to produce a salt of citric acid.

(F) Producing a compound readily hydrolyzable to citric acid or itssalts by converting 3-carbamoyl-3-hydroxy-4-halobutyric acid or a saltor ester thereof to a salt or ester of 3-carbamoy1-3,4-epoxybutyric acidby a reaction with a base, and converting the salt or ester of3-carbamoyl-3,4-epoxybutyric acid to a salt or ester of3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with cyanide.This last named compound is readily hydrolyzed to citric acid by acidichydrolysis or to citric acid salts via basic hydrolysis.

It can be seen from the foregoing that numerous new and highly usefulintermediates are formed in the above process. Accordingly, thisinvention also provides as new compositions the following:

(I) 3-cyano-3-hydroxy-4-halobutyric acid and the alkali metal, alkalineearth metal and ammonium salts thereof, particularly the compositionswhere the 4-halo group is 4-chloro. Salts of the alkali metals arepreferred, particularly the sodium and potassium salts. The free aciditself is particularly preferred.

(II) 3carbamoyl-3-hydroxy-4-halobutyric acid and the salts thereof,particularly the compositions where the 4- halo group is 4-chloro. Thefree acid and the alkali metal thereof, particularly the sodium andpotassium salts, are preferred.

(III) 3-carbamoyl-3,4-epoxybutyric acid and the alkali metal, alkalineearth metal and ammonium salts thereof, preferably the free acid or thealkali metal salts, particularly the sodium and potassium salts.

(IV) 3-carbamoyl3-hydroxy-4-cyanobutyric acid and the alkali metalaalkaline earth metal and ammonium salts thereof particularly the saltsof the alkali metals, especially the sodium and potassium salts.

(V) 3hydroxy3,4-dicarbamoylbutyric acid and the alkali metal, alkalineearth metal and ammonium salts thereof particularly the sodium,potassium, calcium and magnesium salts.

(VI) 3-carbamoyl-3-hydroxyglutaric acid and the alkali metal, alkalineearth metal and ammonium salts thereof particularly the sodium,potassium, calcium and magnesium salts.

DETAILED DESCRIPTION OF THE INVENTION As noted above, in a preferredembodiment of the present invention a preferred starting material is a3-oxo-4- halobutyryl halide such as 3-oxo-4-chlorobutyryl chloride. Thismaterial is readily obtained by a halogenation of diketene, a reactionthat proceeds readily at temperatures from about 20 C. to about 30 C.For further details reference may be had to U.S. Pat. 2,209,683. Ingeneral, in the process sequence involving reactions (l) through (4)above, use of chlorine compounds is preferred because of their excellentproperties in subsequent processing, low cost, and ease of formationinitially. It is readily appreciated that the halogen in the compoundsof the early stages of the present process is primarily useful as a lowcost conveniently displaceable functional group. Compounds containingother functional groups that have the desired properties are also usefulin this connection such as: sulfonates, sulfates, nitrates, nitrites,phosphates and phosphites.

The 3-oxo-4-halobutyryl halide is converted into 3-oxo- 4-halobutyricacid by reaction with water in a hydrolysis type reaction. Surprisingly,this reaction proceeds quantitatively and at a high rate. Preferably, itis conducted in the presence of the same solvent system that existed inthe prior halogenation reaction. The acid product formed at this pointis insoluble in the solvent systems described so that is readilyprecipitates. Hydrogen halide (HC1), the other product of thehydrolysis, evolves as a vapor phase composition. Accordingly, thesolvent, as well as the product acid, is readily separated for furtherprocessing of the acid and recycle of the solvent. A typical recoveryoperation for the acid is ltration or centrifuging to provide theintermediate 3oxo4halobutyric acid in high purity. The hydrolysisoperation occurs readily in virtually 100 percent yield and conversionat a low temperature, typically from about to about 50 C. using a 25percent solution of the halide in carbon tetrachloride solvent. Water isfed in about stoichiometric proportions. A typical solvent is carbontetrachloride.

The 3-oxo-4-halobutyric acid thus obtained is then reacted in an HCNsystem that may contain ammonium, alkali or alkaline earth metal ions aswell as cyanide ions. If the system contains approximatelystoichiometric or a greater amount of ammonium, alkali or alkaline earthmetal ions, the acid is converted to a corresponding ammonium, alkali oralkaline earth metal salt while the 3-oxo group is converted to acyanohydrin. This reaction is typically accomplished by feeding hydrogencyanide and alkali metal cyanide or alkaline earth metal cyanide.Alternately, the cyanide compound may be fed without feeding HCN andlikewise hydrogen cyanide may be fed together with merely a source ofthe metal ions such as an alkali or alkaline earth metal hydroxide,oxide carbonate or bicarbonate or HCN can be fed to either 3-oxo-4-halobutyric acid or its salt or ester. The preferred proportions for thereaction where it is desired to make the salt are generally theequivalent of feeding one mol of alkali metal cyanide or one-half mol ofalkaline earth metal cyanide per mol of 3oxo4halobutyric acid.Frequently, it is desirable to enhance yields by using an excess of HCNin the system ranging up to about 3 mols of excess HCN per mol of3-oxo-4halobutyric acid. A typical feed in such cases is l mol of3-oxo-4-chlorobutyric acid, one mol of sodium cyanide and l/2 mol ofHCN. It will be evident that this results in the feed of an extra halfmol of cyanide per mol of 3-oxo-3-halobutyric acid; however, it has beendiscovered that this excess cyanide provides a substantial increase inthe reaction rate and extent at this stage and in the next step to bedescribed hereinafter and that the excess cyanide is readily recoveredafter the subsequent step for recycle. On the other hand, preferredproportions for producing the cyanohydrin acid directly range from l to4 mols of HCN per mol of 3-oxo-4-halobutyric acid.

Typically in an alkali metal cyanide system the 3-oxo- 4-halobutyricacid fed is reacted to a salt and an HCN addition occurs concurrently inthe same environment wherein a 25 wt. percent solution of3-oxo-4-chlorobutyric acid in -water is combined with enoughconcentrated NaCN solution to produce a pH of from about 5 to about 7.This produces sodium 3-cyano-3-hydroXy-4-chlorobutyrate. Similarly,potassium-3-cyano-3hydroxy4chloro butyrate, calciumbis-3-cyano-3-hydroxy-4-chlorobutyrate, and corresponding compounds ofthe other alkali and alkaline earth metals or of ammonia are formed byfeeding the cyanide salt of the corresponding metal or of ammonia.

The butyrate salt from the preceding step is then reacted with acid toconvert the salt to a butyric acid compound. Usually this isaccomplished by adding a mineral acid to the solution from the precedingstep, dropping the pH to about 2.0. Typically, concentrated HCl is used.This step is omited Where the preceding step was performed with HCN asthe main source of cyanide avoiding the formation of a salt requiringacidification.

'I'he overall yield for the preceding two reactions beginning with the3oxo4halobutyric acid to produce the 3- cyano 3-hydroxy-4-halobutyricacid is about 85 percent when the excess HCN is not used in the iirstreaction.

This yield rises to about 99 percent when using a system ratioequivalent to a feed 0f approximately 0.5 mol of HCN per mol of alkalimetal cyanide and per mol of 3- oxo-4-halobutyric acid. Under theseconditions, the conversion of 3-oxo-4-halobutyric acid to the3-cyano-3-hydroxy-4-halobutyric acid is virtually quantitative as is thereaction of the 3-oxo-4-halobutyryl halide to produce 3-oxo-4-ha1obutyric acid. It is thus seen that the foregoing reactions ofthe present process starting with diketene to produce 3cyano-3-hydroxy-4-halobutyric acid can be caused to occur readily inhigh yield generally better than percent overall.

One of the advantages of having the 3cyano3 hydroxy-4-ha1obutyric acidat this point of the process is that a solvent extraction using ether asa typical solvent is possible to remove by-product salt produced whenalkali metal cyanide, alkaline earth metal, cyanide or ammonium cyanideis fed as the source of cyanide in the formation of the3-cyano-3-hydroxy-4-halobutyrate to provide a purified butyric acidcompound. The acid can be recovered from the extract by evaporation ofthe solvent. The extract or the acid may be hydrolyzed directly bymerely adding water, producing 3-carbamoyl-3-hydroxy4halobutyric acid.The reaction is suitably performed at a temperature of from about 0 toabout 100 C. A temperature of about 40 to about 60 C. is preferred forthis hydrolysis, the hydrolysis being substantially faster than at about35 C.

The system is allowed to achieve its inherent pH for the acid which isfrom about 1/2 to about 4 (measured at -35 C.) depending upon theconcentration which usually ranges from about 2 to about 30 wt. percentsolution of acid in water. A preferred pH range for a solution of 'about10-20 wt. percent concentration is 1.5 to 2.5. Where a salt is fed, thepH is preferably adjusted by adding mineral acid to provide the pHcorresponding to the acid solution of comparable concentration. Ingeneral, it is desired to avoid a pH which is more acidic than about2.() because then the carbamoyl groups hydrolyze to carboxyl groups.

After hydrolysis of the 3cyano group to a 3-carbamoyl group, the3-carbamoyl-3-hydroxy-4-halobutyric acid solution is typically heated at30-40 C. under vacuum to remove water and residual solvent. Theintermediate acid obtained at this point is of comparatively highpurity. Apparently, any unreacted 3-oxo-4-halobutyric aciddecarboxylates during the hydrolysis of the 3cyano3hydroxy-4-halobutyric acid and is removed as a volatile by-product inthe vacuum distillation.

In one type of alternate processing, the solvent extraction and recoveryoperations for the 3cyano3hy droxy-4-chlorobutyric acid are omitted, the3-carbamoyl- 3-hydroxy-4halobutyric acid solution resulting afterhydrolysis being used directly in the subsequent reaction step describedhereinafter leaving the removal of any inorganic salt present at thatpoint for a subsequent part of the process.

The 3 carbamoyl-3-hydroxy-4-halobutyric acid resulting from thepreceding hydrolysis reaction with or without co-present salt isconverted to 3carbamoyl3,4epoxy butyric acid or its salt by a reactionwith a suitable base as defined herein. An aqueous solution of the3-carbamoyl-3-hydroxy-4-halobutyric acid (one mol) (2-30 wt. percentconcentration), typically 10 percent, is combined per 2 equivalent molsof base (typically supplied as a 5 molal aqueous NaOH solution). Thereaction proceeds rapidly, usually being complete in 30 minutes or lessat room temperature. The reaction is suitably performed at temperaturesfrom about 0 to about 100 C., producing the salt.

The intermediate 3carbamoyl3,4 epoxybutyric acid may be recovered incomparatively pure form by acidication of the corresponding salt withmineral acid, by cooling, and or solvent extraction if desired.

summarizing a typical epoxidation and subsequent epoxide cleavageprocedure, 3 carbamoyl-3-hydroxy-4- halobutyric acid is reacted with twoequivalents of base (typically NaOH) per mol of acid at about roomtemperature in aqueous solution forming sodium 3-carbamoyl-3,4-epoxybutyrate. This salt is then reacted with a strong acid(typically HC1) to produce 3-carbamoyl-3,4epoxy butyrate acid which isonly moderately soluble in cold water. Thus, a crystallization processcan be performed at this point if desired to remove by-product salt(NaCl) present in the system.

Following the reaction with base and the purification described if thelatter is used, 3 carbamoyl-3,4epoxybutyric acid salt derived from theresulting salt-free acid is reacted with cyanide ions to open theepoxide ring forming an alkali metal or alkaline earth metal salt of3carbamoyl-3hydroxy4cyanobutyric acid. Preferably, if3-carbamoyl-3,4-epoxybutyric acid is used, it is prereacted with base toform a salt prior to the reaction with cyanide ions. The cleavage of theepoxide also may be accomplished by feeding sodium cyanide and hydrogencyanide together with pH control or buffer components to maintain adesired pH. This reaction liberates up to 1 mol of NaOH per mol ofsodium 3-carbamoyl-3-hydroxy- 4-cyanobutyrate formed.

A preferred pH range for the reaction is from about 9 Yto about 13.5. Aparticularly preferred range is from about 11.0 to about 13.2. Apreferred sequence is to add one mol of alkali metal cyanide (NaCN) or.the equivalent quantities of alkali or alkaline earth metal hydroxide orcarbonate and hydrogen cyanide or other cyanide sources per mol of3-carbamoyl-3,4-epoxybutyrate. As this system reacts, base (NaOH) (1mol) is liberated which produces a gradually increasing pH unless pHcontrol is used. A pH of 14 may be exceeded unless acid is added orother pH control is used to neutralize the system to maintain thedesired pH. Typically, pH is measured with a glass electrode pH meterand the reaction is conducted for from about 1 to about 24 hours at atemperature of from about 10 to about 100 C.

In an alternate procedure which may be preferred in some instances wheresalt removal is not required at this point, the3-carbamoyl3-hydroxy-4-halobutyric acid is reacted with base usuallyproducing at least in part 3- carbamoyl-3-hydroxy-4-halobutyric acidsalt. This system is reacted with cyanide ions and alkali metal oralkaline earth metal ions without going through the intervening acidstage of 3-carbamoyl-3,4-epoxybutyric acid and attendant separations andeven without isolation of 3- carbamoyl3,4epoxybutyric acid salt. Such asequence permits economies in the amount of base required andconsequently in the amount of overall mineral acid required for ultimateconversion t a citric acid product. In a typical example of thisalternate procedure, the 3- carbamoyl-3-hydroxy-4-halobutyric acid isfed in a 2-30 percent, typically 10 percent, mixture in water which iscombined with a base (typically a molal NaOH solution) in about a 1:2molar ratio. After an initial reaction of approximately 1A hour,approximately one mol equivalent of cyanide and metal or ammonium ions(typically a 5 molal solution of NaCN) is added per mol of acidinitially used. The resulting mixture is then agitated for from about 3to about 4 hours at from about 35 to about 40 C. to effect substantiallycomplete conversion to sodiurn 3-carbamoyl-3hydroxy4cyanobutyrate.

It will be appreciated that the foregoing reactions with base and withthe cyanide ions and with the ammonium, alkali metal or alkaline earthmetal ions are suitably conducted in either batch or continuousprocesses in one or more steps or stages under similar or differentconditions.

The foregoing reactions are also suitably performed in a continuous owarrangement wherein the selected reactants such as base, sodium cyanideand acid are added continually.

The 3-carbamoyl-3-hydroxy-4-cyanobutyrate salt produced by the foregoingreactions is then hydrolyzed in an aqueous system preferably with acidor base present. Acid hydrolysis is usually preferred if it is desiredto produce citric acid directly whereas basic hydrolysis is usuallypreferred to produce salts of citric acid when it is desired to avoidgoing through citric acid as an intermediate. Hydrolysis can be completein one stage or operation to produce citric acid or salts of citricacid; however, it may be carried on in a plural step or plural stageoperation with the production and separation or recovery of variousintermediates.

In some instances it is desirable to feed initially less than astoichiometric amount of acid or base hydrolysis reactant to bring abouta partial conversion, leaving complete conversion to a subsequent stepwhere additional reactant is fed. This is particularly helpful withbasic hydrolysis to minimize by-product formation.

In some instances, partial conversion products drop out of solution asinsoluble monoor di-carboxylate precipitates, particularly when alkalineearth metal salts are formed in basic hydrolysis.

In some instances, basic hydrolysis appears to proceed through cyclicimide structures which subsequently cleave to a dicarbamoyl hydroxycarboxylic acid salt and thence to citric acid.

lll Z- O O OH In general, the citric acid yield of the reaction in anacid hydrolysis when using excess acid at temperatures of from about50-250 C., preferably from about 75 to about 150, typically about C. atreux of HC1 (coustant boiling is virtually stoichiometric, typically 98percent or higher. Such a high yield makes acid hydrolysis preferable inmany instances even where citric acid salts are desired iinal products.`On the other hand, acidic hydrolysis suffers from the disadvantage ofproduction of more inorganic salts and hence is less preferred wherethis is an imporant factor. Acidic hydrolysis is followed by aneutralization with a base when it is desired to produce citric acidsalts to enhance purification operations or as a nal product. As withmost of the other reaction steps described in the foregoing, severaldifferent intermediate stages are experienced in an acidic hydrolysis sothat in effect several different reactions take place in sequence. Thus,one may deliberately seek to perform an acidic hydrolysis in two or morestages or steps; for example, an acidic hydrolysis at a pH of from about1.5 to 3.0 to form a hydroxy dicarbamoyl acid or other acidicintermediate followed by a caustic hydrolysis at pH of 8-14, preferably13.5-14, to convert the hydroxy dicarbamoyl acid or other intermediateto a citric acid salt.

It is evident that the three sequential reactions of epoxide formation,epoxide cleavage and basic hydrolysis can occur coincidentally at leastto some extent. In general, different conditions, particularly withregard to pH, are preferred for the different reactions where maximumyields, minimum by-products and maximum rates are desired. On the otherhand, it is possible, for example, to react 3-carbamoyl3-hydroxy 4chlorobutyric acid, base (NaOH) and cyanide (NaCN) in about a 1:2:1molar ratio in a single system at a temperature of from about 25 toabout 35 C. and at a pH of from about 8 to about 14 for from about 3 toabout 72 hours to produce a hydrolysis intermediate, then adding anothermol of base and hydrolyzing the intermediate to trisodium citrate at atemperature of from about 35 to about 100 C. Although such a procedureis preferred where simplicity is important, the generally poor yieldsusually make this procedure less desirable than in the embodiments thatprovide more complete separation of the three steps.

It will be appreciated that numerous additional variations of thepresent invention are possible now that the overall chemistry andrequirements for the various intermediates necessary to produce citricacid and its salts has been discovered. Some of these Variations,permutations and combinations are exemplified in the followingdiscussion.

AMPLIFIED DESCRIPTION WIIH REFERENCE TO THE FIGURES With reference nowto FIG. 1 of the drawing, the process indicated in block form therein isa preferred embodiment of the present invention providing a process forproducing citric acid or its salts from a comparatively low cost andreadily available starting material, diketene. It will be appreciated bythose skilled in the art that diketene is readily obtained by pyrolysisof acetic acid or acetone to produce ketene and that ketene is readilydimerized to produce diketene. In the process of FIG. l the diketene isreacted at with a halogen, typically chlorine to produce3oxo-4-halobutyryl halide, typically 3-oxo-4-chlorobutyryl chloride(B[C]).

The 3-oxo-4-halobutyry1 chloride obtained from halogenation 10 isreacted with water at 11 in a hydrolysis reaction to produce3-oxo-4-halobutyric acid, typically 3-oxo-4-chlorobutyric acid (C[C] (H)At 12, the 3-oxo-4-chlorobutyric acid is reacted with ammonium, alkalimetal or alkaline earth metal ions and with cyanide ions in an aqueoussystem to produce a salt of 3oxo4chlorobutyric acid (C[C] (M)) and HCN.The salt of 3-oxo-4-chlorobutyric acid and the HCN in turn react furtherto form a salt of 3-cyano- 3-hydroxy-4-chlorobutyric acid (D[C] (M) Thesalt of 3-cyano-3-hydroxy-4-chlorobutyric acid is acidiiied with amineral acid at 13 to produce 3-cyano- 3-hydroxy-4-chlorobutyric acid(B[C] (H)) and a salt of the mineral acid and the cations reacted at 12with the 3-oxo-4-chlorobutyric acid.

To enhance the purity of the final product, it is preferred that3-cyan0-3-hydroxy-4-chlorobutyric acid be separated from the saltproduced at 13 providing a saltfree water hydrolysis at 15. Theseparation of salt is readily performed when desired by a solventextraction process 14, a typical solvent being ether. The ether solventdissolves the 3-cyano-3hydroxy4achlorobutyric acid following Whih theacid is recovered from the solvent by vaporizing the ether solvent.Temperatures at steps 11- 14 are from about 0 C. to about 50 C.,preferably from about to about 35 C. To minimize hydrolysis of cyanogroups to carbamoyl groups prior to hydrolysis at 15, it is usuallypreferred that the temperatures of 11-14 be below about 30 C.

In an alternate procedure, the 3oxo4chlorobutyric acid from 11 isreacted at 12 directly with HCN in the absence of ammonium or metalcations to produce 3- cyano-3-hydroxy-4-chlor0butyric acid for feed tohydrolysis step 15.

The cyano group of 3-cyano-3-hydroxy-4-chlorobutyric acid recovered at14 or of the acid from a direct HCN reaction at 12 is then hydrolyzed at15 to a carbamoyl group to produce 3-carbamoyl-3-hydroxy-4-chlorobutyricacid (B[C] (H) Water is a suitable hydrolyzing reactant.

The 3-carbamoyl-3-hydroxy-4-chlorobutyric acid produced at 15 is thenconverted to a salt of 3-carbamoyl- 3,4-epoxybutyric acid (F(M)) byreaction with a base in a ring formation reaction at 16.

The ring structure salt compound formed at 16 in the reaction with thebase is converted at least partially to 3-carbamoyl-3,4-epoxybutyricacid (F(H)) by reaction with a mineral acid at 17. Preferably, themineral acid used is a strong inorganic acid, typically hydrochloricacid. Strong organic acids, typically acetic acid, or oxalic acid arealso suitable but generally less desirable because of greater expenseper mol. This conversion to acid is desirable for one or more of severalreasons. One reason is that this provides a way to remove at 18by-product inorganic salt produced at 16 since the 3-carbamoyl-3,4epoxybutyric acid is moderately soluble in Water at low temperatures ofthe order of 20 C. Thus, the 3-carbamoyl3,4epoxybutyric acid may berecovered by a crystallization technique to provide an intermediatebutyric acidcompound having a reduced salt content.

If this purification is not desired, a partial acidification may stillbe used at 17 to provide a mixed acid-salt system feed for the next step19 to facilitate pH control in step 19.

The 3-carbamoyl-3,4-epoxybutyric acid or acid-salt mixture obtained from18 is converted at 19 in a complex series of interrelated reactionpreviously described in detail to produce a salt of3-carbamoyl-3-hydroxy-4-cyanobutyric acid (G(M)). The amount of acidneeded to be fed at this point is minimized by controlling the acid/salt ratio in the mixed product from 17, particularly in a continuoussystem; however, some acid addition is usually desired at 19 in batchsystems to counteract the tendency toward increasing pHs brought aboutby the release of base (NaOH) in the course of the reaction.

The salt of 3-carbamoy1-3-hydroxy-4-cyanobutyric acid (G(M)) obtainedfrom 19 is then hydrolyzed at 20 with a strong base to produce a citricacid salt (K(M)). Such hydrolysis produces a salt of citric aciddirectly. In one of numerous alternate hydrolysis procedures, the saltof 3- carbamoyl-3-hydroxy-4-cyanobutyric acid is hydrolyzed at 20 withstrong acid, preferably a mineral acid such as hydrochloric acid, toproduce citric acid (K(H) Where the salt of citric acid is a moredesired product of a desired acidic hydrolysis than is citric aciditself, the citric acid is readily neutralized with a base to producethe desired citric acid salt of the base. A typical base used for such ahydrolysis at this point is sodium hydroxide to produce trisodiumcitrate. Similarly, tripotassium citrate is produced by using potassiumhydroxide and mixed sodium potassium salts can be produced by usingmixed sodium and potassium oxides or hydroxides.

The recovery of product citric acid or citric acid salts from thehydrolysis efl'luent is suitably accomplished by any of severalseparation and purification operations. The purification of citric acidyby calcium salt precipitation is of course well known in connection withprocessing of natural source citric acid and it may be used here, ifdesired; however, it is usually adequate and less expensive to use otherprocedures such as a selective crystallization of trisodium citrate in acyclic process involving the precipitation of by-product sodium chlorideor other such organic or inorganic salts.

FIG. 2 of the drawing shows broadly several key steps of the presentprocess. The blocks indicated by reference characters 16', 19 and 20indicate two reacting or converting stages plus a step of hydrolyzingand correspond generally to similarly numbered steps in FIG. 1.

The feed to converting step 16 is one or more of several particularlyuseful intermediates (E) for the preparation of citric acid; viz,3carbamoyl-3-hydroxy-4-halobutyric acid (E(H)) or a salt (E(M)) or ester(E(R)) thereof. The feed is reacted at 16 with a base to produce a salt(F(M)) or ester (F(R)) of 3-carbamoyl3,4epoxybutyric acid.

In general, the rst action of the base fed at 16 is to convert any3-carbamoyl3-hydroxy4-halobutyric acid E(H) present into a salt of theacid E(M), typically a soduim salt where sodium hydroxide is used as thebase fed to step 16. Thereafter, the process step at 16 is a reaction ofa salt or ester of 3carbamoyl3hydroxy4 halobutyric acid to eliminatehalogen and form an epoxide. If desired, step 16 may be preceded by aseparate step wherein 3-carbamoyl-3-hydroxy-4-halobutyric acid isconverted to a salt or ester or this may be a portion of step 16 itself.

The salt or ester of 3-carbamoyl-3-hydroxy-4-halobutyric acid thenreacts with base, typically the sodium hydroxide mentioned or othersuitable base disclosed herein to eliminate the 4-halogen and thehydrogen of the S-hydroxy group (l) liberate water, (2) form .a3,4-epoxy compound and (3) form a salt of the halogen present in the3-carbamoyl-3-hydroxy-4-halobutyric acid and of the cation of the baseused in the reaction. ITypically, the salt formed at (3) is NaCl.

The reaction at 16 is not particularly critical or sensitive withrespect to pH as long as the conditions are suiciently basic for thereactions to occur but not s basic as to produce undesired reactionssuch as destroying the ester if retention of the ester form is desired.Thus, in general, batchwise addition of the base used is permissibleunless a progressive addition of the base is desired to maintain as higha pH as possible and at the same time minimize converson of the ester.Of course, it is understood that the quantity of base and the conditionsinvolved can be selected so as to deliberately convert an ester feedinto a salt at this step if such is desired. A preferred feed to 16 isthe acid or the salt, particularly the former because such is morereadily obtained by preferred prior processing. The reaction using thisfeed material is conducted at a temperature from about 5 to about 100 C.in from about one minute to about three hours time.

The second step of the process of FIG. 2 is the converting step 19wherein the salt or ester of 3-carbamoyl- 3,4-epoxybutyric acid obtainedfrom the preceding step 16' is converted to a salt or ester of3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with cyanide.This step is preferably conducted in an aqueous system having a basic pHbut not so basic as to convert the ester form to the salt form unlesssuch conversion is specitically desired at this step.

The salt or ester produced at 19 is then hydrolyzed at 20 to producecitric acid or a salt of citric acid such as trisodium citrate.Typically, the citric acid or salt product is produced in hydrated form,usually the dihydrate, with the pentahydrate usually less preferred.

The hydrolysis reaction at 20 usually occur in two or more steps orstages producing numerous intermediates. It is evident that converting asalt or ester of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid to citricacid requires the conversion of at least two functional groups, viz, acyano group andv a carbamoyl group. Where the feed to the hydrolysis isin the ester form, the hydrolysis in addition involves the conversion ofthe ester structure into an acid or salt structure liberating thealcohol constituency of the ester fed. Usually, the liberation of thisalcohol provides a further complication in the somewhat involvedrecovery of the product citric acid or citric acid salt because of thenecessity to recover the alcohol for economic or purification of productreasons. Avoidance of such problems makes the use of esters at thispoint generally less desired than the use of salts except where estersminimize adverse side reactions.

Typical acids preferred for hydrolysis 20, as well as at 19, 17, and 13in FIGS. l and 2 are hydrochloric acid, hydrobromic acid, sulfuric acid,phosphoric acid and nitric acid. These are strong acids having anionization constant K of 1x10-4 or stronger. Of these acids, the halogenacids are frequently preferred because a preferred process for producingthe starting compound, namely, 3-carbamoy1-3-hydroxy-4-halobutyric acid,involves the use of halogen so that process convenience and economiessuggest a system balance around the halogen or freedom from otherforeign substances. Thus, a particularly preferred mineral acid for usein hydrolysis is hydrochloric acid. Other strong acids, includingorganic. acids such as acetic acid and oxalic acid, with onzationconstants K greater than about 1x105 are also usable at 20, 19, 17 and13.

An acid hydrolysis 20 proceeds rapidly and to a high degree ofcompletion in a single environment at a temperature of from about C. toabout 150 C. in from about l to about 48 hours.

A base hydrolysis proceeds to a high degree of completion in a singleenvironment at a temperature from about 15 C. to about 150 C. in fromabout 1 to about 72 hours. To enhance equilibria, it is occasionallydesired that even where hydrolysis 20 is suitably conducted in a singleenvironment, that it be conducted in a staged manner under dilerentconditions in the different stages. Such staging typically facilitiesthe removal of by-products such as ammonia produced in the hydrolysis.Although the hydrolysis is suitably conducted in a batchwise manner inone or more stages, it may also be conducted in a continuous manner inone or more stages in which case a staging arrangement is convenientlyprovided `by using a tower type of countercurrent of co-current flowcontacting device, typically a falling-film type of reactor or a packedtower or a preforated plate type of tower such as those used indistillation or absorption operations. A preferred contactingarrangement is a packed tower or a perforated plate tower operative atatmospheric pressure, subatmospheric pressure or super-- atmosphericpressure equipped with provision for a stripping operation such as withsteam supplied from an external source or locally generated by means ofa reboiler arrangement at the bottom of the tower with feed of the3-carbamoyl-3-hydroXy-4-cyanobutyric acid salt or ester at the top ofthe tower. Such a flow arrangement provides for efficient productremoval or recovery stripping of ammonia liberated in basic hydrolysis.Other useful stripping gases are those reasonably inert or not adverselyreactive in the environment, including air, nitrogen, carbon dioxide, asWell as hydrocarbons such as methane, ethane, propane, butane, hydrogenand the like.

An alternate hydrolysis of the 3-carbamoyl-3-hydroxy- 4-cyanobutyricacid salt or ester at 20 of PIG. 2 is a basic hydrolysis usingappropriate org-anic or inorganic bases with the inorganic basesgenerally preferred. -In addition to the basic hydrolysis procedurespreviously described, another arrangement for basic hydrolysis is whatis termed a water hydrolysis accomplished by feeding essentially waterutilizing the by-product ammonia liberated in the course of the reactionas a source of cations for converting the citric acid to ammonium salts.In general, such a water hydrolysis and hydrolysis using by-product ordeliberately fed ammonia or ammonium compounds such as hydroxides andcarbonates is so slow as to be in the less preferred category since evenwhere ammonium salts of citric acid are the desired product, it isusually preferred to first proceed through an acid hydrolysis asdescribed in the foregoing and follow it with a neutralization withammonia or an 'ammonium compound.

In other alternate hydrolysis procedures, the fundamental hydrolysis isconducted in two steps in an acidic or basic hydrolysis to hydrolyzefirst one of the cyano and the carbamoyl groups following which theresultant product from the first hydrolysis is subjected to a secondhydrolysis conversion of the second one of said groups. It is generallyparticularly preferred that where such a two-step hydrolysis isemployed, the lirst group to be hydrolyzed is the cyano group ratherthan the carbamoyl group because the presence of the carbamoyl groupappears to be highly desirable to bring about a rapid and completehydrolysis of the cyano group, particularly in basic hydrolysis.

To assist basic hydrolysis and minimize the amounts of base required,the base liberated at the epoxide ring scission operation 19 can beutilized in the subsequent hydrolysis without separation orneutralization by acid for pH control at 19. Thus, the operations at 19can be cornbined with at least an initial portion of the hydrolysis 20.

To do this it is desirable to avoid the operation use of acid in pHcontrol at the epoxide cleavage operation 19. This provides anincidental benefit in a reduction of the amount of salt that must beseparated from the final product.

-By feeding to 19 the salt of 3-carbamoy1-3,4epoxy butyric acid inapproximately a 1 molar solution or less concentrated, the maximumachievable caustic concentration in the system will also beapproximately l molar, corresponding to a pH of about 14. Thus the pHmay be limited by controlling the concentration of cyanide and3-carbarnoyl-3,ll-epoxybutyric acid salt without requiring feed of acidfor pH control.

Letters used in the figures identify the ions involved in the varioussystems. For example, B is 3-oxo-4-halobutyrylhalide, C is the3-oxo-4-halobutyrate ion, C[C] is the 3oxo4chlorobutyrate ion, D[C]R isan R ester of 3cyano-3-hydroxy-4-chlorobutyric acid, E[C] (H) is3carbamoyl-3-hydroxy-4-chlorobutyric acid, F(M) is a3-carbamoyl-3,ll-epoxybutyrate salt, G(M) is a3-carbamoyl-3hydroxy-4-cyanohutyrate salt, K is citrate radical, K(H) iscitric acid, and KOM) is a citrate salt.

FIG. 3 indicates in a general way the process 11 of FIG. 1 where3-oxo-4-halobutyryl halide is hydrolyzed to produce 3-oxo-4-halobutyricacid or a salt or ester thereof. Preferably, the hydrolysis is areaction with water. In a preferred embodiment this step receives3-oxo-4-chlorobutyryl chloride and produces 3-oxo-4-chlorobutyric acidby a hydrolysis reaction with Water. Although chlorine feed compoundsare preferred, other suitable halogen compounds may be used provided thefeed compound reacts with water to produce a correspondingoxo-halobutyric acid or alternately with alcohol to produce an ester.Thus, other feed compounds for the hydrolyzing step 11 include3-oxo-4-bromobutyryl bromide, 3oxo-4- iodobutyryl iodide, and3-oxo-4-uobutyryl fluoride.

`Using the other halogen compounds as feed to reactant step 11 insteadof the chloro compounds exemplified produces corresponding butyrates,typically 3-oxo-4-bromobutyric acid, 3-oxo-4-iodobutyric acid and3-oxo-4-uobutyric acid.

It will be recognized that, although water is a preferred hydrolysisreactant for producing 3-oxo-4-halobutyrate radicals, because of theconvenient reactivity and loW cost, other hydrolysis reactants includingacids or bases may be suitable and desirable. For example, thehydrolysis 11 may be conducted with an aqueous solution containing basicreacting cations such as ammonium, alkali metal or alkaline earth metalcations. This produces corresponding salts of 3oxo4-halobutyric aciddirectly such as sodium 3-oxo-4-chlorobutyrate.

Other typical compounds produced by a hydrolysis 11 includeammonium-3-oxo-4-chlorobutyrate, potassium-3- oxo 4 chlorobutyrate,lithium-3-oxo-4-chlorobutyrate, magnesium-bis-3-oxo-4-chlorobutyrate,calcium-bs-B-oxo- 4chlorobutyrate, strontium bis 3-oxo-4-chlorobutyrate,barium-bis-3-oxo-4-chlorobutyrate as well as similar salts of the otheralkali metals and alkaline earth metals as well as similar saltscontaining the other halogens in place of chlorine.

A wide variety of esters can be produced from acids produced at 11including esters of various primary, secondary and tertiary, straightchain, branched chain, monocyclic, polycyclic, saturated, unsaturated,aromatic monobasic, dibasic and polybasic alcoholic compounds. Preferredesters include primarily the esters of alcohols having from l to about20 carbon atoms per molecule, more preferably esters of the loweralkanols having up to about six carbon atoms per molecule. Thus, typicalesters are those of methyl, ethyl, propyl, isopropyl, butyl, isobutyl,secondary butyl, tertiary butyl and the various pentyl and hexylalcohols. Typical diol esters include mono and diesters of ethyleneglycol, propylene glycol, butanediol and the like. Thus, typicalspecilic esters include ethyl-3-oxo-4- chlorobutyrate,methyl-3-oxo-4-bromobutyrate, methyl-3- oxo-chlorobutyrate,propyl-3-oxo-4-iodobutyrate, isopropyl-3-oxo-4-uobutyrate, and the like.Although such ester compounds may not be similarly described in suchdetail for each of the subsequent steps in the overall process of thepresent invention, it is to be understood that starting esters thusproduced at an early point in the process can be carried through toproduce similar corresponding esters as well as salts of the variousother acids as well as the acids themselves described in connection withthe other steps of the overall process.

In many instances mixed acid-salt, acid-ester, salt-ester, oracid-salt-ester systems can exist in various proportions at this and atsubsequent steps of the process depending on the pH of the varioussystems and upon the proportions in which the reactants are used. Suchcompositions based on the acids, salts and esters described hereinprovide novel compositions of matter in themselves.

With reference now to FIG. 4 of the drawing, the cyanohydrination orcyanohydration reaction step 12 of the present process is indicated. Inthis reacting step 12, 3-oxo-4-halobutyric acid or a salt thereof issubjected to reaction with hydrogen cyanide or a salt thereof to produce3cyano-3-hydroxy-4-halobutyric acid or a salt thereof.

Salts of hydrogen cyanide useful include ammonium, alkali metal andalkaline earth metal cyanides, such as ammonium cyanide, sodium cyanide,potassium cyanide, calcium cyanide, and magnesium cyanide.

In this step 3oxo4halobutyric acid or a salt thereof is reacted withcyanide and hydrogen ions.

This process 12 may include an acidification (13 of FIG. l) to produce3cyano3-hydroxy-4-halobutyric acid from the corresponding salt. Thus,3-oxo-4-halobutyric acid is reacted with a cyanide of ammonia, of analkali metal, or of an alkaline earth metal to produce an ammonium,alkali metal or alkaline earth metal salt of 3- oxo-4-halobutyric acidand HCN. In turn, the salt of 3- oxo-4-halobutyric acid is reacted withhydrogen cyanide to produce the corresponding ammonium, alkali metal oralkaline earth metal salt of 3-cyano-3-hydroxy-4-halobutyric acid. Thesalt of 3-cyano-3-hydroxy-4-halobutyric acid is reacted with a strongacid to produce 3-cyano-3- hydroxy-4-halobutyric acid and an ammonium,alkali metal or alkaline earth metal salt of the strong acid.

Preferably the amount of hydrogen cyanide available to the system is anamount in excess of that released by the reaction of the3-oxo-4-halobutyric acid with the cyanide salt.

In a preferred embodiment 3-oxo-4-halobutyric acid is reacted with HCNto produce 3-cyano-3-hydroxy-4-halobutyric acid.

A preferred feed is one or more of the keto acids described as productsof the hydrolysis 11 of FIG. 3. It is to be understood, however, thatthe source of the 3-oxo- 4halobutyrate radicals used as feed forreacting step 12 of FIG. 4 is not limited to the process described inconnection with FIG. 3 since feed 3-oxo-4-halobutyric acid obtained fromany source or prior processing history is generally suitable feed forcyanohydrination as long as the purity thereof is acceptable for thereaction at 12 and the utilization of the products of that reaction.

It is to be appreciated, of course, that the process of FIG. 3 is apreferred way of producing feed acid for the cyanohydrination step 12 ofFIG. 4. Thus, a particularly preferred feed for FIG. 4 is a3-oxo4halobutyric acid such as 3oxo4chlorobutyric acid obtained from theprocess of FIG. 3 when using water as a hydrolysis reactant.

Reacting step 12 of FIG. 4 forms a cyanohydrin structure at the oxofunctional group of the feed 3-oxo-4-halobutyric acid or salt. Thus, aprimary requirement for this reaction system is that it provide for theaddition of hydrogen and cyanide to 3-oxo-4-halobutyrate radicals toproduce corresponding 3-cyano-3-hydroxy-4-halobutyrate radicals. Thisreaction is suitably conducted in a wide variety of ways underconditions ranging from basic through neutral to acidic. If thecyanohydrination 12 of FIG. 4 is conducted in an aqueous system wherethe reactants fed to the step include a source of metal cations, saltproducts D(M) are formed from an acid feed. The preferred cations ofsuch salt products of 12 are the alkali and alkaline earth metals.Typical preferred product compositions from reacting step 12 of FIG. 4include sodium, potassium, magnesium, or calcium salts of 3-cyano-3-hydroxy-4-halobutyric acid, the halogen of such salts being anyhalogen, preferably chlorine.

Where metal cations are not available, the product from cyanohydrination12 is usually an acid, such as 3- cyano-3-hydroxy-4-chlorobutyric acid.Such acid is obtained, for example, by reacting hydrogen cyanide withfeed 3-oxo-4-chlorobutyric acid in an aqueous system containing fromabout 1 to about 30 wt. percent HCN and from about 1 to about 30 wt,percent 3-oxo-4-chlorobutyric acid at from about Oto about 100 C.

In addition, 3oxo4halobutyrate esters may be employed as feed tocyanohydrination 12 of FIG. 4. Such esters are preferably converted tosalts at 12. Where acids are desired, they may be obtained byacidification of the salts.

With reference now to FIG. of the drawing, the process step thereinindicates a hydrolysis operation wherein the cyano group of3-cyano-3-hydroxy-4-halobutyric acid or a salt or ester thereof ishydrolyzed to a carbamoyl group to produce 3-carbamoyl-3-hydroxy-4-halobutyric acid or an ester thereof. This hydrolysis is suitablyconducted at a pH of from about V2 to about 4 or even up to about 6.5.The hydrolysis is preferably conducted under acidic conditions no moreacidic than a pH of about 2 with acid feed to avoid decompositions ofthe cyano group and conversion of the 3-carbamoyl group to a 3-carboxylgroup. Thus, a preferred feed to hydrolysis 15 is3-cyan0-3-hydroxy-4-halobutyric acid and a preferred hydrolyzingreactant is water at a pH of from about 2 to about 4 producing3-carbamoyl-3-hydroxy-4- halobutyric acid.

Typical acids produced in this way are 3-carbamoyl3hydroxy-4-chlorobutyric acid, 3carbamoyl3hydroxy4- bromobutyric acid,3-carbamoyl-3-hydroxy-4-iodobutyric acid and3-carbamoyl-3-hydroxy-4-uobutyric acid. Although such processing usuallyis in a less preferred category, the hydrolysis of the cyano group alsomay be conducted when feeding corresponding esters and evencorresponding salts in which case the hydrolysis usually operates undermore nearly neutral conditions; however, even here it is preferred thatbasic conditions be avoided.

Cil

Where permissible, the maintenance of acidic conditions may be enhancedwhen feeding esters and salts by the feed of a mineral acid as definedherein or other suitable acids of the type used as catalysts in esterformation. A typical acid is HCl.

Other typical compounds produced by hydrolysis 15 includemethyl-3-carbamoyl-3hydroxy-4-chlorobutyrate,sodium-3carbamoyl-3-hydroxy-4-bromobutyrate,isopropyl-3-carbamoyl-3-hydroxy-4-butyrate.

FIG. 6 indicates a converting-reacting step 16, In this step3-carbamoyl-3-hydroxy-4-halobutyric acid or a salt or ester thereof isconverted to a salt or ester of 3-carbamoyl3,4epoxybutyric acid by areaction with a base. In this operation any free acid present isneutralized to produce a generated salt and then said generated salt orsaid salt or ester is converted to a structure containing a 3,4-epoxygroup by dehydrohalogenation. Although the preferred material epoxidizedat 16 is a salt or ester, particularly the former such as3-carbamoyl-3-hydroxy-4- chlorobutyric acid salt obtained byneutralization of the acid from step 15 of the process of FIG. 5, thefeed to 16 for epoxidation is also suitably the acid, additional basecations being provided to 16 to provide the salt equivalent.

In any event, 3carbamoy13-hydroxy-4-halobutyrate radicals are reacted at16 with a base as herein defined to form 3 carbamoyl 3,4 epoxybutyrateradicals. Also formed at this step is by-product salt derived fromreaction of the cation component of the base with the halogen of thefeed 3carbamoyl3-hydroxy-4-halobutyrate radicals.

For the complete conversion of feed acid to 3-carbamoyl-3,4epoxybutyrateacid salt, 2 mols of an alkali metal or ammonium base or 1 mol of analkaline earth metal base is used per mol of feed3-carbamoyl-3-hydroxy-4- halobutyric acid. Of course, it is evident thatthe foregoing amount of base required for the production of3-carbamoyl-3,4epoxybutyric acid, salt or ester is reduced by half wherethe feed to converting step 16 is already in salt or ester form unlessof course it is desired that the converting step 16 also convert anester feed into a salt product in which case the full number ofequivalents of basic reacting substance is required. Although inorganicbases such as the hydroxides, oxides, carbonates and bicanbonates of thealkali or alkaline earth metals are preferred for reaction at 16, strongorganic bases such as quaternary ammonium hydroxides or ion exchangeresins having fixed cationic sites are also useful at 16 to producecorresponding salts of the organi-c base where such salts are desired asa specific product or as an intermediate for use in a subsequent step ofthe present citric acid process.

It will be appreciated from the foregoing discussion that uponcompletion of the epoxidation of converting step 16 of FIG. 6., thevariety of the earlier compositions with regard to halogen content is nolonger evident. Thus, in general, the 3-carbamoyl-3,4-epoxybutyrateradicals pro duced at 16 are substantially independent of the halogenconstituency of the preceding compounds. On the other hand, it is to beobserved that cost is usually a significant factor in the production ofany chemical composition and that therefore a preferred halogenconstituent of the preceding compounds is one that will produce the3-carbamoyl-3,4epoxybutyrate radicals at the lowest price. From suchconsiderations as these, it is generally preferred that the halogencompounds which precede the 3-carbamoyl-3,4-epoxybutyric acid bechlorine cornpounds or, to a lesser extent, bromine compounds.

In step 19 of FIG. 7 a salt or ester of 3carbamoyl3,4 epoxybutyric acidis converted to a salt or ester of 3-carbamoyl-3-hydroxy-4-cyanobutyricacid via reaction with cyanide. Preferably, the reaction is under basicconditions and in an aqueous system. Preferably, the system containsammonium, alkali metal or alkaline earth metal cations in an amount ofat least two ammonium or alkali metal cations or one alkaline earthmetal cation per 3car bamoyl3,4epoxybutyrate anion and at least onecyanide cation per 3-carbamoyl-3,4-epoxybutyrate anion. Hydroxide ionsare formed in the reaction. As discussed in connection with FIGS. 1 and2 in some instances a preferred feed for step 19 to assist in pH controlis a 3-carbamoyl- 3,4epoxybutyrate acid/salt mixture. Typically, atleast a part of each of the cyanide ions and the ammonium, alkali metalor alkaline earth metal cations is provided by feeding a chemicalcompound containing both, typically an alkali metal cyanide, or byfeeding two compounds such as HCN and alkali metal hydroxide or HCN andalkali metal cyanide.

Thus, typical feed to converting step 19 of FIG. 17 is a3-carbamoyl-3,4-epoxybutyrate in acid, salt or ester form or a mixtureof two or more of the acid, salt or ester while the correspondingproduct from the step is a 3-carbamoyl-3-hydroxy-4-cyanobutyrate salt orester or mixture of salt and ester.

FIG. 8 indicates a coordinated two-step operation where the first stepis the epoxidation or converting-reacting step 16 described inconnection with FIG. 6 and the second step is the epoxide cleavage ofconvertingreacting step 19 described in connection with FIG. 7. Thisfigure shows the coordination in which the converting-reacting step 16of FIG. 6 receives acid, ester or salt feed to produce the epoxide saltor ester intermediate which intermediate is fed directly to theconverting-reacting step 19 for cleavage of the epoxide to form cyanoand hydroxy structures to produce 3-carbamoyl-3-hydroxy-4-cyanobutyricacid, salt or ester. The system of the figure may operate with the saltform throughout, receiving a salt form at the feed to 16, providing asalt form product from 19.

FIGS. 9 and 10 indicate hydrolysis details. These figures compare aone-step hydrolysis process (FIG. 9) in which3-carbamoyl-3-hydroxy4cyanobutyric acid, salt or ester is converteddirectly to citric acid in an acidic hydrolysis or to a citric acid saltin a basic hydrolysis versus a plural step hydrolysis process (FIG. inwhich one or more intermediates are formed. FIG. 10 illustrates feedingpart of the hydrolyzing reactant or reactants (acid or base) at step 25and feeding at step 26 another part of hydrolyzing reactant or reactantsrequired for the hydrolysis. This illustrates numerous variations inintermediates formed in the process; such as, 3hydroxy3,4dicarbamoylbutyric acid and its salts and esters,2-carbamoylmethyl-Z-hydroxy succinic acid and its salts or esters, and3-carbamoyl-3-hydroxyglutaric acid and its salts or esters. In addition,this stepwise conversion also represents the various esters andsalt-esters of citric acid that result when using ester feed tohydrolysis 25.

The various intermediate compositions involved in this last part of theprocess as well as elsewhere in the process have independent utilityother than for use in carrying on the present process to produce citricacid. In general, all of the compositions have useful surface activeproperties themselves as detergents or builders, for example, andprovide useful intermediates for other reactions because ofthe numerousfunctional groups contained therein. Since all of the intermediatecompositions contain carboxyl groups, they are useful to form esters, asplasticizers, as intermediates for use in other reactions, and innumerous similar and related applications. Among the salt compositionsproduced, the salts of the alkali and alkaline earth metals are usuallypreferred, particularly salts of the former category such as salts ofsodium or potassium.

The reactions of the present process are for the most part ionicreactions in liquid reaction media in which the systems behave asmixtures of the various ions present rather than as individualcompounds. The preferred liquid reaction media or solvent for thepresent largely ionic process is water because it is readily available,is low in cost and has excellent solubility properties for the variousreactants and intermediates invOlVGd. Other protic solvents such asalcohols and alcohol-water mixtures are also useful, particularlyalkanols, typically methanol, ethanol, and methanol-water orethanol-water mixtures. Similarly, glycols provide useful solvents,alone or in admixture with water. Typical glycol systems includeethylene glycol, propylene glycol, and ethylene glycol-water mixtures.

The use of the ester form of the intermediates expands the variety withregard to solvent or diluent systems to include systems containing othermaterials such as substituted and unsubstituted cyclic, acyclic andaromatic hydrocarbons including parains, oleins, ethers, ketones,aldehydes, esters, water immiscible alcohols, alkanols, and the like.

In the several steps of the process where solvents are used for purposesother than as reaction media, for example, in solvent extraction,preferred solvents have been mentioned as ether, particularly diethylether, aectone, methanol, as well as hydrocarbon such as pentane,hexane, and the like. With regard to the solvent systems useful for thehalogenation of diketene, preferred solvents are low boiling solventsfor the diketene which are inert to the reactants under the conditionsof use such as carbon tetrachloride, ethylene dichloride, propylenedichloride, and carbon disulfide.

In a sense, with ionic systems, the distinctions between the variousforms of categories of acid, ester and salt may in some instances dependon extrinsic factors such as pH of the system and on the presence ofother materials. Some of the reactions disclosed require certain acidityvalues in order to proceed at acceptable rates whereas with some of thecompounds it is important to avoid certain acidity values to avoidundesired side reactions.

Since the molecules of the present compositions involve severalfunctional groups closely associated, there are interactions thatpromote unexpected reactions and which inhibit some expected reactions.Thus the present compositions and compounds exhibit a high degree ofunpredictability as far as the properties of the various individualfunctional groups are concerned as well as with regard to the propertiesof the compounds themselves. As a practical matter, in several instancesthe present invention utilizes interactions of the functional groups toassist desired reactions and suppress other reactions.

The following examples indicate preferred embodiments of the presentinvention.

EXAMPLE I yPreparation of 3-oxo-4-chlorobutyric acid A solution of3-oxo-4-chlorobutyryl chloride was prepared by passing in 0.645 mol ofC12 gas into a solution of 0.645 mol of diketene at 20 C. in1,2-dichloroethane which was approximately solvent by volume. Thestarting diketene was of approximately 98.1 percent purity as assayed byNMR spectroscopy. The solution was then treated in a three neck flaskfitted with thermometer, dropping funnel, condenser, mechanical stirrerand a N2 inlet and outlet with 11.8 ml. of water (0.655 mol) addedslowly from the dropping funnel. A slow stream of N2 gas was passedthrough the flask and allowed to pass out the condenser and into a NaOHsolution prepared from ml. of 7.93 N NaOH (0.635 mol) diluted toapproximately 800 ml. The water was added with vigorous stirring at sucha rate that no HC1 escaped the NaOH trap while maintaining a temperatureof 25-30 C. in the reaction mixture. The product acid began tocrystallize from the reaction mixture about 1/3 of the way through theaddition of water. After completion of the addition, stirring wascontinued overnight. The NaOH trap solution was then made up to 1 literand a 100 ml. aliquot removed. This was titrated to a phenolphthaleinend point requiring 3.23 ml. of 0.1043 -N HC1 showing a net excess of3.36 milliequivalents of unused base remained. This corresponds to a99.08 percent yield of HC1 based on diketene. The solid acid wasrecovered by iltration and yielded 61.1 g. (70.8 percent of theory) ofsnow white crystalline product, M P. 69-71 C. Further washing of theflask with pentane removed 1.32 g. of solids. 21.3 g. of acid wasrecovered upon evaporation of the residual solvent ltrate at roomtemperature on a rotary evaporator under vacuum. Both solid productswere Washed with pentane and found to be pure via their NMR spectra. Thecombined yield was 83.7 g. or 97 percent of theory. The melting pointreported by Rosdig, 'Kleppe and Markl is 6769 (Ben, 95 1252 (1962)).

Preparation of 3-cyano-3-hydroxy-4-chlorobutyric acid 68.8 g. of3-oxo-4-chlorobutyric acid (94.2 percent purity by NMR) (0.476 mol) wasmixed with 200 ml. of distilled Water in a three neck ilask tted wih athermometer, dropping funnel, stirrer and connected via an ice condenserto a nitrogen bubbler which was connected to a NaOH trap in series.Sodium cyanide (24.5 g.) (0.50 mol) was dissolved in 75 ml. of water andplaced in the dropping funnel. Th'e contents of the flask were cooled inan ice bath and the NaCN solution added at -15 C. to give a pH of 8. Themixture was brought to a pH of 0.8 with 46 ml. (0.568 mol) concentratedHC1 and then extracted with five 100 ml. portions of ether. The combinedether extract was dried with anhydrous MgSO4. After filtering off thedrying agent and washing the solids with ether, the ether was evaporatedon a rotary evaporator at 35-40" C. Assay of the 78.3 g. of product byNMR showed 80.6 percent 3-cyano-3- hydroxy-4-chlorobutyric acid, 8.22percent water, 3.53 percent acetoacetic acid and 7.6 percent ether. Thelast traces of ether and water were quite diflicult to remove. The yieldwas 82 percent.

Preparation of 3-carbamoyl-3-hydroxy-4-chlorobutyric acid 68.27 g. (0.5mol) of 3oxo4chlorobutyric acid was placed in 200 ml. of Water. To thiswas added a solution of 24.5 g. (0.5 mole) NaCN in 75 ml. of water at10-15 C. from a dropping funnel. The resulting pH was 5.9. AdditionalNaCN solid (0.3 gram) was dissolved in the reaction mixture to give a pHof 7.8. After 30 minutes, 44 ml. of concentrated HCl (about 1/2 mol) wasadded to bring the pH to 1.0. The reaction mixture was then extractedwith seven 100 ml. portions of ether and the ether extracts combined.The ether solution was dropped into 200 ml. of water at 50 C.,distilling the ether 01T as rapidly as it could be condensed. Theaqueous solution was heated for 165 minutes at 50 C. after etherdistillation ceased. The NMR spectrum showed that essentially all of thecyanohydrin had been converted to the corresponding carbamoyl compound.The aqueous solution was placed in a continuous ether extractor andallowed to extract overnight. During this time 19.2 g. of3-carbamoyl-3-hydroxy-4-halobutyric acid crystallized from the reboiler.

The remaining aqueous solution was stripped under high vacuum on arotary evaporator heated to maintain a temperature of 2030 C. Thecontents of the flask became solid and after being broken up wastransferred to a vacuum desiccator where drying was completed. Thecombined weight of solids was 64.0 g. or 88.8 percent ield.

y A sample was titrated to a phenolphthalein end point. 0.19475 g.required 7.70 ml. of 0.1326 N NaOH corresponding to an equivalent weightof 190.7 (theory: 181.6). This is probably slightly high due to residualmoisture as well as due to indicator color change at 9 to 11 whereas atitration curve indicates a neutralization end point at a pH=7.7.Elemental analysis of a recrystallized sample gave the followingresults.

Wt. percent Theory Found C 33. 07 32. 48 H 4. 44 4. 12 N 7. 71 7. 96

Preparation of 3-carbamoyl-3,4-epoxybutyric acid 235.6 g. of3-carbamoyl-3-hydroxy4-chlorobutyric acid (96.0 percent assay) (1.25mols) which had been recrystallized from acetone was suspended in 800ml. of water and g. of NaOH dissolved in 100 ml. of water (1.25 mols)was added while maintaining the temperature at about 15 C. After '1/2hour, the pH was brought to about 2 by the addition of concentrated HCl(approximately 1.25 mols). The mixture was cooled to about 5 C.whereupon solid 3-carbamoyl-3,4-epoxybutyric acid slowly crystallized.After 2 hours, 62.3 g. of pure solid product was obtained in 34 percentyield. Assay of solutions showed essentially quantitative conversion ofthe 3-carbamoyl 3-hydroxy-3-chlorobutyric acid to 3-carbamoyl-3,4-epoxybutyric acid.

Preparation of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid 43.5 g. (0.3mol) of the 3-carbamoyl-3,4-epoxybutyric acid was placed in ml. of waterand 50.2 ml. of 5.28 M NaOH solution (0.3 mol) added at 15 C. The pH ofthe solution was 12.07. 16.2 g. of NaCN (0.33 mol) dissolved in 50 ml.of water was then added at 15 C. The pH changed to 12.28. Thetemperature was then raised to 33-35 C. over about 10 min. 6.73 N HCl(approximately 0.3 mol) was then added slowly to maintain the pH at 11.After 27 hrs. the solution was assayed by NMR analysis and showed a1011-2 percent yield of the 3- carbamoyl-3hydroxy4cyanobutyric acidsalt.

Preparation of trisodium citrate 30.0 ml. of a 0.60 M (0.018 mol)solution of sodium 3-carbamoyl-3-hydroxy-4-cyanobutyrate, 0.6 M in NaCl(0.018 mol) was mixed with 3.1 ml. of a 5.98 M NaOH solution (0.0186mol) giving a pH of 13.22. After standing for 261A. hrs. a 20 ml.aliquot (0.0108 mol) was removed. Addition of 2.1 ml. of 5.98 M NaOH(0.0108 mol) to the aliquot followed by heating'the mixture 17 hrs. at100 C. gave 3.89 solids containing sodium citrate and sodium chloride onevaporation and drying in a vacuum desiccator. The theoretical weight is3.85 g. The NMR spectrum of the solution prior to evaporation showedessentially pure citrate with traces of acetate. This assay indicated94.4 mol percent citrate and 5.6 mol percent acetate.

EXAMPLE II A 50 percent (Wt.) solution of diketone in carbontetrachloride was prepared. Chlorine in diluent nitrogen (mol ratio1Cl2z3N2) was bubbled in at 20 C. and about 1 atmosphere pressure untilchlorination was complete. The product was 3-oxo-4-chlorobutyrylchloride.

To a stirred ask at 30 C. containing 3oxo4chloro butyryl chloride incarbon tetrachloride resulting from halogenation as in the previousexample, a stoichiometric amount of Water was added in a dropwisemanner. An insoluble precipitate of 3oxo4chlorobutyric acid was formedand recovered by filtration. HC1 was liberated and evolved as a gas.

A 25 wt. percent aqueous solution of 3-oxo-4-chlorobutyric acid wasprepared and a concentrated (6.7 molal) solution of sodium cyanide inwater was added slowly to produce a system with a pH of 6-7. Thisproduced an aqueous solution of sodium3-cyano-3-hydroxy-4-chlorobutyrate.

To the solution of sodium 3-cyano-3-hydroxy-4-halobutyrate was addedconcentrated HC1 to drop the pH to about 1.0 forming 3cyauo-3-hydroxy-4-chlorobutyric acid.

The 3-cyano-3-hydroxy-4-chlorobutyric acid was then extracted from thewater using diethyl ether to separate the product acid from by-productNaCl.

The ether extract was then added to water at 50 C. to hydrolyze thecyauo group to the carbamoyl group producing 3carbamoyl-3-hydroxy-4-chlorobutyric acid. The system was then subjectedto vacuum evaporation at 30-40 C. producing a high, purity product in anoverall yield of 86 percent from the 3-oxo-4-chlorobutyric acid. Theyield from diketone to 3-oxo-4-chlorobutyric acid was virtuallyquantitative.

A 10 percent by weight solution in water of3-carbamoyl-3hydroxy-4-chlorobutyric acid was then prepared. To this wasadded a molal aqueous solution of NaOH in proportions of one mol of acidper two mols of NaOH. The solution was stirred for '1/2 hour at 35-40 C.The product 3-carbamoyl-sodium 3,4-epoxy butyrate was allowed to remainin solution. The yield as determined by NMR was virtually quantitative.

To this solution of sodium 3-carbamoyl-3,4-epoxybutyrate was added a 5molal aqueous solution of NaCN in proportions of 3 mols per mol of3-carbamoyl-sodium 3,4- epoxybutyrate. The system was agitated for about4 hours at 35-40" C. The yield to sodium 3-carbamoyl-3- hydroxy-4cyanobutyrate was virtually quantitative as determined by NMR.

The sodium 3 carbamoyl 3-hydroxy-4-cyanobutyrate was then acidhydrolyzed to citric acid by the addition of an equal volume ofconcentrated HCl. The system was gently heated at -100 C. for about 7hours in an open beaker. During this heating time the volume was reducedto about one-fourth of the original volume. The solution was thenevaporated to dryness under vacuum and the solids extracted withacetone. Evaporation of the acetone extract gave a syrup of citric acidwhich was taken up in methanol and neutralized with sodium methoxide toprecipitate trisodium citrate. The product was relatively pure andwhite.

The foregoing reactions were analyzed at each step by NMR to determineprogress and conrm a substantial absence of side reactions.

EXAMPLE III Preparation of sodium-3-carbamoyl-3,ll-epoxybutyrate 29.3grams of 3-cyano-3-hydroxy-4-chlorobutyric acid of 88 percent puritycontaining 12 percent diethyl ether from an ether extraction of productfrom a prior reaction was added to 50 grams of water at 25 C. and thenthe resulting mixture was heated to 55 C. for 3 hours. Following this,the heat was removed and the solution cooled to about 35 C. in 30minutes. The resulting product 3- carbamcyl-4-hydroxy-4-halobutyric acidwas analyzed by NMR (nuclear magnetic resonance) showing 2 AB patternsat -3.75 (the 4-chloromethyl structure) and at -2.85 (the methylene inthe 2-position).

The 3 carbamoyl-3-hydroxy-4-halobutyric acid from the preceding step wasstirred in an ice bath and kept there while a solution of 12.8 grams ofsodium hydroxide in 20 rnl. of water was added over a 15 minute periodwith cooling. After 45 minutes, the product was analyzed by NMRindicating substantially complete formation of epoxide (AB patterncentered at -2.705, J=17 Hz.).

EXAMPLE IV Preparation of sodium-3-carbamoyl-3-hydroxy- 4-carbamoylbutyrate A 3.05 gram (21 millimols) sample of 3carbamoyl3,4-epoxybutyric acid Was neutralized with 1.78 grams (21 millimols) ofsodium bicarbonate in ml. of water. Then 3 drops of Thymol blue (pH8.0-9.6) were added. Then 1.09 grams (2l millimols) of sodium cyanide in5 ml. of water was added over a 10 minute period. During 24 this period5 molar acetic acid was added dropwise to hold the pH at about 9.1.

NMR analysis was made after 1 hour showing decreasing epoxide AB patternalong with decreasing 2 position methylene of the epoxide and withincreasing 2 position methylene of 3-carbamoyl-3-hydroxy-4-cyanobutyricacid salt (-4 Hz. upeld from the 2 position methylene of the startingepoxide) and with increasing cyanomethylene.

The foregoing composition was allowed to stand at room temperature forapproximately 3 hours. The pH had increased to 10.5. Acetic acid wasadded to drop the pH to 9.1. NMR analysis was again run showing furtherepoxide decrease and further increase of the cyanide derivative.

The sample was then allowed to stand at room temperature forapproximately 15 hours and again analyzed by NMR. Virtually all epoxidespectra had disappeared, the cyauo compound content had decreased andnew spectra appeared indicating the presence of a different structure.The new spectra was identied as characteristic of the product obtainedby conversion of the cyauo group to the carbamoyl group.

EXAMPLE V Preparation of citric acid A 50 ml. beaker equipped with amagnetic stirrer and a glass electrode pH meter was charged with 2.89grams (20 millimols) of 3-carbamoy1-3,4-epoxybutyric acid and 10 ml. ofwater. Potassium carbonate (1.38 grams, 10 millimols) was added to formpotassium-3-carbamoyl-3,4 epoxybutyrate. The temperature was 35-36 C.

To this was added' 1.35 grams (20 mmols) of potassium cyanide in oneportion with stirring. The pH was monitored continuously with the pHmeter and controlled at 9.70 to 9.80 by adding 5 molar acetic aciddropwise.

After 15 minutes another 1.35 grams (a second mol equivalent) ofpotassium cyanide was added.

After a total of 130 minutes from the rst addition of potassium cyanide,the system had a pH of 6.5 and by NMR analyzed only about 5 to 8 percentepoxide content. Then a-hydroxy isobutyric acid was added as an internalstandard. The yield conversion of starting epoxide topotassium-3-carbamoyl-3-hydroxy-4-cyanobutyrate was calculated at thispoint as virtually 100 percent.

After a total of 180 minutes from the initial KCN addition, with the pHat 6.5, 8 ml. of concentrated HC1 (96 mmol) was added to the mixture andthe resulting mixture at a pH of l was agitated at 55 C. for 18.5 hours.An NMR analysis was then run using an internal standard showing aconversion of 87 percent of the potassium-3-carbamoyl-3-hydroxy-4-cyanobutyrate to citric acid and carbamoylintermediate.

The mixture was stirred another 20 hours at 55 C. to -85 C. After 0.8hour at this temperature, the formation of a white solid precipitate wasnoted. After a total of 4 hours at 80-85, the heating was discontinuedand the mixture allowed to cool to room temperature. 13.26 grams ofliquid was decanted leaving 3.77 grams of solid. The liquid was analyzedby NMR, showing citric acid with residual incompletely hydrolyzedmaterial.

The liquid Was then heated to C. and held at that temperature for about16 hours to complete the conversion to citric acid.

EXAMPLE VI A 40 m1. beaker equipped with a magnetic stirrer was chargedwith 2.90 grams (20.0 millimols) of 3-carbamoyl-3,4epoxybutyric acid.This material was neutralized with 20 millimols of a standard 0.898molar NaOH solution. Then 1.29 grams of percent NaCN (25 millimols) wasadded in one portion and the pH was maintained at 8.0 by adding 5.43molar acetic acid dropwise from a burette. The temperature was 35-36 C.

After minutes the system pH was dropped to 7.1 by additional aceticacid, then stirred overnight at 33 C.

The NMR spectrum indicated 85-95 percent conversion of the sodium3-carbamoyl-3,4-epoxybutyrate to sodium3-carbamoyl-3-hydroxy-4-cyanobutyrate.

The solution was transferred to a ask equipped with a magnetic stirrerand 10 ml. of concentrated HC1 (120 millimols) was added. The solutionwas heated at 110 C. for 4 hours. Additional HCl (5 ml.) was added. Twohours later the solution contained only 5 percent3-carbamoyl-3-hydroxy-4-cyanobutyric acid. At this point an additionalml. of HC1 was added. Two hours later the solution contained only 2percent 3-carbamoyl-3-hydroxy-4-cyanobutyric acid. Hydrolysis wascontinued overnight. Hydorlysis conversion of sodium 3-carbamoyl-3hydroxy-4-cyanobutyrate to citric acid was 98 percent. Overallconversion to citric acid from starting 3-carbamoyl-3,4-epoxybutyricacid was 84 percent.

EXAMPLE VII A 40 ml. beaker equipped with a magnetic stirrer was chargedwith 2.90 grams (20 millimols) of 3-carbamoy1- 3,4-epoxybutyric acid.The acid was neutralized to a pH of 7.0 by adding a 0.898 molar solutionof NaOH. This formed sodium 3-carbamoyl-3,4-epoxybutyrate. Then sodiumcyanide, 1.29 grams (25 millimols) was added in one portion. Thereafterthe pH was maintained at 11.0 by the addition of `6.73 molar HC1.Temperature was 30-31 C.

After 151 minutes an additional 1.29 grams of NaCN was added. After 205minutes from the start, the system was analyzed by NMR showing about 5percent 3-carbamoyl-3,4epoxybutyric acid remaining. The pH was 11.15.

The solution was then heated to 70 C. over a 25 minute period and heldat that temperature for about 35 minutes. The pH dropped to 9.48indicating consumption of caustic. As heating at 70 C. continued, NaOHwas added periodically to maintain a pH of 10.2. After 130 minutesheating at 70 C., NaOH was added to provide a pH of about 14 and thesystem was heated overnight at 75 C.

The system was cooled, methanol added, and the solids filtered providing5.4 grams of a white free flowing product.

What is claimed is:

1. A process for producing citric acid or salts thereof which comprises:

(1) converting 3carbamoy13-hydroxy-4-halobutyric acid or a salt or esterthereof to a salt or ester of 3- carbamoyl-3,4-epoxybutyric acid by areaction with a base,

(2) converting the salt or ester of 3-carbamoyl-3,4- epoxybutyric acidto a salt or ester of 3-carbamoyl- 3-hydroxy-4-cyanobutyric acid viareaction with cyanide, and

(3) hydrolyzing the salt or ester of3-carbamoyl-3-hydroxy-4-cyanobutyric acid to produce citric acid or asalt thereof.

2. A process according to claim 1 which comprises:

(1) converting 3-carbamoyl-3-hydroxy-4-halobutyric acid or a saltthereof to a salt of 3-carbamoyl-3,4- epoxybutyric acid by reaction witha base,

( 2) converting the salt of 3-carbamoyl-3,4-epoxybutyric acid to a saltof 3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with cyanide,and

(3) hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyric acidto produce citric acid or a salt thereof.

3. A process according to claim 1 which comprises:

( 1) converting 3-carbamoyl-3-hydroxy-4-chlorobutyric acid to a salt of3-carbamoyl-3,4-epoxybutyric acid by reaction with a hydroxide, oxide,carbonate or bicarbonate of an alkali metal or an alkaline earth metal,

(2) converting the salt of 3-carbamoyl-3,4-epoxybutyric acid to a saltof 3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with an alkalimetal or alkaline earth metal cyanide, and

(3) hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyric acidto produce citric acid or a salt thereof.

4. A process according to claim 1 which comprises:

(1) converting 3-carbamoyl-3-hydroxy-4-chlorobutyric acid to an alkalimetal salt of 3-carbamoyl3,4-epoxy butyric acid by reaction with analkali metal hydroxide,

(2) converting the alkali metal salt of 3-carbamoyl-3,4

epoxybutyric acid to an alkali metal salt of3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with an alkalimetal cyanide, and

(3) hydrolyzing the alkali metal salt of 3-carbamoyl3-hydroxy-4-cyanobutyric acid with a strong mineral acid to producecitric acid.

5. A process according to claim 1 which comprises:

(l) converting 3-carbamoyl-3-hydroxy-4-chlorobutyric acid to an alkalimetal salt of 3-carbamoyl-3,4epoxy butyric acid by reaction with analkali metal hydroxide,

(2) converting the alkali metal salt of 3-carbamoyl-3,4

epoxybutyric acid to an alkali metal salt of 3-carbamoy1-3-hydroxy-4-cyanobutyric acid via reaction with an alkalimetal cyanide, and

(3) hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyric acidwith alkali metal hydroxide in an aqueous system to produce an alkalimetal salt of citric acid.

6. A process according to claim 1 wherein said 3-carbamoyl-3-hydroxy-4-halobutyric acid or a salt or ester thereof is3-carbamoyl-3-hydroxy-4-chlorobutyric acid or a salt or ester thereof.

7. A process according to claim 1 which comprises:

(1) converting 3-carbamoyl-3-hydroxy-4-halobutyric acid or a saltthereof to a salt of 3-carbamoyl3,4- epoxybutyric acid by reaction in anaqueous system with a water soluble base having an ionization constantof at least 10-6 mols per liter,

(2) converting the salt of 3-car-bamoyl-3,4epoxy butyric acid to a saltof 3-carbamoyl-3-hydroxy-4- cyanobutyric acid via a reaction in anaqueous system with a water soluble inorganic cyanide compound, and

(3) hydrolyzing the salt of 3-carbamoy1-3-hydroxy-4- cyanobutyric acidto produce citric acid or a salt thereof.

8. The process of claim 1 wherein the reaction in step (2) is performedat a pH in the range of from about 9 to about 13.5.

9. A process according to claim 1 which comprises:

(1) converting 3-carbamoyl-3-hydroxy-4-chlorobutyric acid or a saltthereof to a salt of 3-carbamoyl-3,4 epoxybutyric acid by reaction in anaqueous system with NaOH or KOH or both,

(2) converting the salt of 3-carbamoyl-3,4epoxybutyric acid to a salt of3-carbarnoyl-3-hydroxy-4- cyanobutyric acid via a reaction in an aqueoussystem at a pH of about 11.0 to about 13.2 with sodium cyanide orpotassium cyanide or both, and

(3) hydrolyzing the salt of 3-carbamoyl-3-hydroXy-4- cyanobutyric acidto produce citric acid or a salt thereof.

10. A process for |producing citric acid or salts thereof whichcomprises:

( 1) converting 3-carbamoyl-3,4-epoxybutyric acid or a salt or esterthereof to 3-carbamoyl-'3-hydroxy-4- cyanobutyric acid or a salt orester thereof by a reaction with cyanide, and

(2) hydrolyzing 3-carbamoyl-3-hydroxy-4-cyanobutyric acid or a salt orester thereof to produce citric acid or a salt thereof.

11. A process for producing citric acid or salts thereof which compriseshydrolyzing 3carbarnoyl3hydroxy4 cyanobutyric acid or a salt or esterthereof.

12. The process of claim 11 wherein the hydrolysis is conducted withmineral acid to |produce citric acid.

13. The process of claim 11 wherein the hydrolysis is conducted withmineral acid to produce citric acid and wherein the citric acid isneutralized with a hydroxide, oxide, carbonate or bicarbonate of analkali metal or an alkaline earth metal to produce a salt of citricacid.

14. The process of claim 11 wherein the hydrolysis is conducted with analkaline earth metal hydroxide, oxide, carbonate or bicarbonate toproduce an insoluble precipitate and the precipitate is subsequentlyconverted to citric acid by reaction with a mineral acid.

15. The process of claim 11 wherein the hydrolysis is conducted with analkaline earth metal hydroxide, oxide or carbonate to produce aninsoluble precipitate and the precipitate is subsequently converted to asoluble salt by reaction with ammonia, ammonium hydroxide or carbonateor an alkali metal oxide, hydroxide, carbonate or bicarbonate, ormixture thereof.

16. A process for producing citric acid or salts thereof whichcomprises:

(1) hydrolyzing the cyano group of 3-carbamoyl-3- hydroxy-4-cyanobutyricacid or a salt or ester thereof to produce3-hydroxy-3,4-dicarbamoylbutyric acid or a salt or ester thereof, and

(2) hydrolyzing the 3-hydroxy3,4-dicarbamoylbutyric acid or its salt orester into citric acid or a salt thereof.

17. A process for producing citric acid or salts thereof which compriseshydrolyzing 3-hydroxy-3,4-dicarbamoylbutyric acid or a salt or esterthereof to citric acid or a salt thereof.

18. A process for producing citric acid or salts thereof whichcomprises:

(1) hydrolyzing the cyano group of 3-cyano-3-hydroxy- 4-halobutyric acidor a salt or ester thereof to produce3-carbamoyl-3-hydroxy-4-halobutyric acid or an ester thereof,

(2) converting the 3carbamoyl-3-hydroxy-4-halo butyric acid or esterthereof to a salt or ester of 3- carbamoyl-3,4-epoxybutyric acid by areaction with a base,

(3) converting the salt or ester of 3carbamoy13,4

epoxybutyric acid to a salt or ester of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with cyanide, and

(4) hydrolyzing the salt or ester of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid to produce citric acid or a salt thereof.

19. A process for producing citric acid or salts thereof whichcomprises:

(1) subjecting 3-oxo-4-halobutyric acid or a salt or ester thereof toreaction with hydrogen cyanide or a salt thereof to produce3-cyano-3-hydroxy-4-halobutyric acid or a salt or ester thereof,

(2) hydrolyzing the cyano group of the 3-cyano-3- hydroxy-4-halobutyricacid or the salt or ester thereof to produce3-carbamoyl-3-hydroxy-4-ha1obutyric acid or an ester thereof,

(3) converting the 3carfbamoyl 3 hydroxy-4-halobutyric acid or the esterthereof to a salt or ester of 3 carbamoyl 3,4 epoxybutyric acid by areaction with a base,

(4) converting the salt or ester of 3carbamoy1 3,4- epoxybutyric acid toa salt or ester of S-carbamoyl- 3 hydroxy 4 cyanobutyric acid viareaction with cyanide, and

(5) hydrolyzing the salt or ester of 3-canbamoyl-3-hydroxy-4-cyanobutyric acid to produce citric acid or a salt thereof.

20. A process for producing citric acid or salts thereof whichcomprises:

(l) hydrolyzing 3 oxo 4 halobutyryl halide to produce 3 oxo 4halobutyric acid or a salt or ester thereof,

(2) subjecting 3-oxo-4-halobutyric acid or a salt or ester thereof toreaction with hydrogen cyanide or a salt thereof to produce3-cyano-3-hydroxy-4-halobutyric acid or a salt or ester thereof,

(3) hydrolyzing the cyano group of 3 cyano 3 hydroxy 4 halobutyric acidor a salt or ester thereof to produce 3 carbamoyl 3 hydroxy 4halobutyric acid or an ester thereof,

(4) converting the 3-carbamoyl-3-hydroxy-4-halobutyric acid or the esterthereof to a salt or ester of 3carbamoyl-3,4-epoxybutyric acid thereofby a reaction with a base,

(5) converting the salt or ester of 3-carbamoyl3,4

epoxybutyric acid to a salt or ester of 3-carbamoyl-3-hydroxy-4-cyanobutyric acid via reaction with cyanide, and

(6) hydrolyzing the salt or ester of the 3-carbamoy1-3-hydroxy-4-cyanobutyric acid to produce citric acid or salt thereof.

21. A process for producing citric acid or salts thereof whichcomprises:

(1) reacting 3-oxo-4-chlorobutyryl chloride with Water to produce3-oxo4chlorobutyric acid,

(2) reacting 3-oxo-4-chlorobutyric acid with cyanide ions and withammonium, alkali metal or alkaline earth metal ions in an aqueous systemto produce a salt of 3-cyano-3-hydroxy-4-chlorobutyric acid,

(3) acidifying the salt of 3-cyano-3-hydroxy-4- chlorobutyric acid toproduce 3-cyano-3-hydroxy-4- chlorobutyric acid and recovering the3-cyano-3- hydroxy-4-ch1orobutyric acid,

(4) hydrolyzing the cyano group of 3cyano3 hydroxy-4-chlorobutyric acidto produce 3-carbamoyl-3-hydroxy-4-chlorobutyric acid,

(5) converting 3-carbamoyl-3hydroxy4chlorobutyric acid to a salt of3-carbamoyl-3,4 epoxybutyric acid by a reaction with a base,

(6) converting the salt of 3carbamoyl-3,4epoxybu tyric acid to a salt of3-carbamoyl-3-h`ydroXy-4- cyanobutyric acid via reaction with cyanide,and

(7) hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyric acidto produce citric acid or a salt thereof.

Z2. A process for producing citric acid or the salts thereof whichcomprises:

(1) reacting 3-oxo-4-chlorobutyryl chloride with water to produce3-oxo-4-chlorobutyric acid,

(2) reacting 3-oxo-4-chlorobutyric acid with ammonium, alkali metal oralkaline earth metal ions and with cyanide ions in an aqueous system toproduce a salt of 3-oxo-4-ch1orobutyric acid and HCN and reacting thesalt of 3-oxo-4-chlorobutyric acid with HCN to form a salt of3cyano-3hydroxy4chloro butyric acid,

(3) acidifying the salt of 3-cyano-3-hydroxy-4-chlorobutyric acid withmineral acid toproduce 3-cyano-3- hydroxy-4-chlorobutyric acid and asalt of the mineral acid,

(4) solvent extracting the 3-cyano-3-hydroxy-4-chlorobutyric acid torecover said acid from the salt of the mineral acid and recovering saidacid from the solvent,

(6) converting the 3-carbamoyl-3hydroxy4chloro butyric acid to a salt of3-carbamoyl-3,4-epoxybutyric acid by reaction with a base,

(7) reacting the salt of 3-carbamoyl-3,4-epoxybutyric acid with mineralacid to convert the salt to an acid structure forming3-canbamoyl-3,4-epoxybutyric acid and a salt of the mineral acid and thebase reacted at step (6),

(8) recovering the 3-carbamoyl-3,4-epoxybutyric acid,

(9) converting the 3-carbamoyl-3,4-epoxybutyric acid to a salt of3-carbamoyl-3hydroxy4cyanobutyric acid by reacting the acid withammonium, alkali metal or alkaline earth metal ions and with cyanideions in an aqueous system at a pH from about 8 to 12, and

(10) hydrolyzing the salt of 3-carbamoyl-3-hydroxy- 4-cyanobutyric acid'with a hydroxide, oxide or carbonate of an alkali metal or alkalineearth metal to produce a salt of citric acid.

23. The process of claim 22 wherein the step (9) conversion of3-carbamoyl-3,4-epoXybutyric acid to a salt of 3 carbamoyl 3hydroxy-4-cyanobutyric acid is performed in two steps of:

(A) the 3-carbarnoyl-3,4-epoxybutyric acid is reacted with a base toform a salt of 3carbamoyl3,4-epoxy butyric acid and then (B) the salt of3-carbamoyl-3,4-epoxybutyric acid is reacted with cyanide ions in anaqueous system at a pH of from about 8 to about 14.

24. A process for producing citric acid or the salts thereof whichcomprises:

(1) reacting 3-oxo-4-halobutyryl halide with water to produce3-oXo-4-halobutyric acid,

(2) reacting 3-oxo-4-halobutyric acid with ammonium, alkali metal oralkaline earth metal ions and with cyanide ions in an aqueous system toproduce a salt of 3-oxo-4-halobutyric acid and HCN and reacting the saltof 3oxo-4chlorobutyric acid with HCN to for-m a salt of3-cyano-3hydroxy4halobutyric acid,

(3) solvent extracting the 3-cyano-3-hydroxy-4-halobutyric acid salt torecover said salt,

(4) hydrolyzing the cyano group of the recovered 3-cyano-3-hydroxy-4-halobutyric acid salt to convert it to a salt of3carbamoyl-3hydroxy4halobutyric acid,

(5) converting the salt of 3-carbamoyl-3-hydroxy-4- halobutyric acid toa salt of 3-carbamoyl-3,4epoxy butyric acid by reaction with a base,

(6) reacting the salt of 3carbamoyl3,4-epoxybutyric acid with mineralacid to convert the salt to an acid structure forming3-carbamoyl-3,4-epoxybutyric acid and a salt of the mineral acid and ofthe base reacted at step (5),

(7) recovering the 3-carbamoyl-3,4-epoxybutyric acid,

(8) converting the 3-carbamoyl-3,4-epoxybutyric acid t a salt of3carbamoyl-3-hydroxy4cyanobutyric acid by reacting the acid withammonium, alkali metal or alkaline earth metal ions and with cyanideions in an aqueous system at a pH of from about 8 to about 14, and

(9) hydrolyzing the salt of 3-carbamoyl-3-hydroXy-4- cyanobutyric acidto produce citric acid or a salt thereof.

25. A process for producing citric acid or the salts thereof whichcomprises:

(1) reacting 3-oXo-4-halobutyryl halide with water to produce3-oxo-4-halobutyric acid,

(2) reacting 3-oxo-4-halobutyric acid with hydrogen cyanide to produce3-cyano-3-hydroxy-4-halobutyric acid,

(3) hydrolyzing the 3cyano-3-hydroxy-4-halobutyric acid with water toproduce 3carbamoyl3hydroxy 4-halobutyric acid,

(4) converting the 3 carbamoyl 3 hydroxy-4-halobutyric acid to a salt of3-carbamoyl-3,4epoxy butyric acid by reaction with a base,

() reacting the salt of 3carbamoyl3,4-epoxybutyric acid with mineralacid to convert the salt to an acid structure forming3-carbamoyl-3,4-epoxybutyric acid and a salt of the mineral acid and ofthe base reacted at step (4),

(6) recovering the 3-carbamoyl-3,4-epoxybutyric acid,

(7) converting the 3-carbamoyl-3,4-epoxybutyric acid to a salt of3-carbamoyl-3-hydroXy-4-cyanobutyric acid by reacting the acid withammonium, alkali metal or alkaline earth metal ions and with cyanideions in an aqueous system at a pH of from about 8 to about 14, and

(8) hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyric acidto produce citric acid or a salt thereof.

26. A process for producing citric acid or the salts thereof whichcomprises:

(1) reacting 3-oxo-4-halobutyryl halide with water to produce3-oXo-4-halobutyric acid,

( 2) reacting 3-oxo-4-halobutyric acid with ammonium, alkali metal oralkaline earth metal ions and with cyanide ions in an aqueous system toproduce a salt of 3-oXo-4-halobutyric acid and HCN and reacting the saltof 3-oxo-4-halobutyric acid with HCN to form a salt of3cyano-3hydroxy4halobutyric acid,

(3) acidifying the salt of 3-cyano-3-hydroxy-4-halobutyric acid withmineral acid to produce 3-cyano-3- hydroxy-4-halobutyric acid and a saltof the mineral acid,

(4) solvent extracting the 3-cyano-3-hydroXy-4-halobutyric acid torecover said acid from the salt of the mineral acid, and recoveringIsaid acid from the solvent,

(5) hydrolyzing the recovered 3-cyano-3-hydroxy-4- halobutyric acid toproduce 3carbamoyl3hydroxy 4-halobutyric acid,

(6) converting the 3-carbamoyl 3 'hydroxy4halobu tyric acid to a salt of3-carbamoyl-3,4-epoxybutyric acid by reaction with a base,

(7) converting the salt of 3-carbamoyl-3,4epoxybu tyric acid to a saltof 3carbamoyl-3-hydroxy-4-cyanobutyric acid by reacting the salt withcyanide ions in an aqueous system at a pH of from about 8 to about 14,and

(8) hydrolyzing the salt of 3-carbamoyl3hydroxy4 cyanobutyric acid toproduce citric acid or a salt thereof.

27. A process for producing citric acid or the salts thereof whichcomprises:

(l) reacting 3-oxo-4-halobutyryl halide with water to produce3-oxo-4-halobutyric acid,

( 2) reacting 3-oxo-4-halobutyric acid with ammonium, alkali metal oralkaline earth metal ions and with cyanide ions in aqueous system toproduce a salt of 3-oXo-4-halobutyric acid and HCN and reacting the saltof 3oxo4halobutyric acid with HCN to form a salt of3cyano3-hydroxy-4-halobutyric acid,

(3) hydrolyzing the cyano group of the salt of 3-cyano-S-hydroxy-4-halobutyric acid Wit-h water and mineral acid to produce3carbamoyl-3-hydroxy-4-halobutyric acid,

(4) converting the 3 carbamoyl-3-hydroxy4-halobu tyric acid to a salt of3-carbamoyl-3,4epoxybutyric acid by reacting with a base,

(5) converting the salt of 3carbamoyl-3,4epoxybu cyanobutyric acid byreacting the salt with cyanide tyric acid to a salt of3carbamoyl3hydroxy4 ions in an aqueous system at a pH of from about 8 toabout 14, and

(6) -hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyric acidto produce citric acid or a salt thereof.

28. A process for producing citric acid or the salts thereof whichcomprises:

(1) reacting 3-oXo-4-halobutyryl halide with water to produce3-oXo-4-halobutyric acid,

(2) reacting 3-oxo-4-halobutyric acid with hydrogen 31 cyanide toproduce 3-cyano-3-hydroXy-4-ha1obutyric acid, (3) hydrolyzing the3-cyano-3-hydroxy-4-ha1obutyric acid with water to produce3-carbamoy1-3hydroxy 4-ha1obutyric acid,

, (4) converting the 3-carbamoyl-3-hydroxy-4-halobutyric acid to a saltof 3-carbamoyl-3,4-epoxybutyric acid by reaction with a base,

(5) converting the salt of 3-carbamoy1-3,4epoxybu tyric acid to a saltof 3-carbamoy1-3-hydroXy-4- cyanobutyric acid by reacting the salt withcyanide ions in an aqueous system at a pH of from about 8 to about 14,and

32 (6) hydrolyzing the salt of 3-carbamoyl-3-hydroxy-4- cyanobutyricacid to produce citric acid or a salt thereof.

References Cited JACS, 72, 5019-5024 (1950).

LORRAINE A. WEINBERGER, Primary Examiner P. J. KILLOS, AssistantExaminer U.S. Cl. X.R.

260--326.3, 348 A, 348.6, 465.4, 483, 484 P, 534 M, 539 R, 544Y P01050UNITED STATES PATENT OFFICE CERTIFICATE OF CRRECTION Patent No.5,769,557 I Dated october 5o, i975 Inventor) Karl Wiegand It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected s shown below' column 4,Equation 5, reads Nc-CHg-C-CHgC-OM O=CNH2 OH Q Column 7, line 5, reads"that vis readily", should read that it readily --5 line 69, reads"omited", should read omitted Column lO, line lill, reads o OH o n nHN=CCH2 JCH2COQ EEN-0:0

0H 0H o I l should read HN=CCHiZC-CHZC-oQ H2N-rC=o column 1i, line 72,rea-ds "whirl", should ready which Column lll, line 22, reads"onzation", lshould read ionization --3 line M2, reads "of co-cur-",should read or co-our- --5 line mi, reads "preforated", should readperforated Column 20, line l?, reads "aectone", should read acetone --5line 75, reads "99,08", should read 99.8 Column 2l, line ll, reads"67-69", v I

gggo l UNITED STATES PATENT OFFICE CERTIFICATE 0F CGRRECTION Patent No.5,769,537 Dated October 50, 1975 Invencorgd) A Karl E. Wiegand Page 2 Itis certified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Should read 67-69C Column 23, line 24, reads "mol of E-carbamoyl-sodiumLL", should read mol of sodium-B-carbamoyl BJL- Column 25, line l5,reads "Hydorlysis", should read Hydrolysis Column 30, line 6N, reads"cyanobutyric acid by reacting the salt with cyanide", should read tyricacid to a salt of 5-carbamoyl-B-hydroxy-lf- --5 line 65, reads Htyricacid to a salt of' -carbamoyl-B-hydroxy-Ll-"', should read,

-- cyanobutyric acid by reacting the salt with cyanide Signed and sealedthis 16th day of' April 197A.

(SEAL) Attest: x

C. IVIARSHALL DANN EDWARD ILFLLTCHERJH. v

Commissioner of Patents Attesting Officer

